Systems and methods for epicardial navigation

ABSTRACT

Systems and methods for navigating a catheter along the epieardial surface of the heart are disclosed. At least some of the embodiments disclosed herein are useful for epieardial ablation, Various embodiments permit ablation of the epieardial surface of the heart using an external ablation catheter in the pericardial space and an internal guide catheter within the heart. Such a configuration allows the clinician to precisely target for ablation specific locations on the cardiac tissue.

PRIORITY

The present application is related to, and claims the priority benefitof, International Patent Application Serial No. PCT/US2008/000834, filedJan. 23, 2008, which: (1) is related to, claims the priority benefit of,and in at least some designated countries should be considered acontinuation-in-part of, International Patent Application Serial No.PCT/US2007/015239, filed Jun. 29, 2007; (2) is related to, claims thepriority benefit of, and in at least some designated countries should beconsidered a continuation-in-part of, International Patent ApplicationSerial No. PCT/US2007/015207, filed Jun. 29, 2007; and (3) is relatedto, and claims the priority benefit of, U.S. Provisional PatentApplication Ser. No. 60/881,839, filed Jan. 23, 2007. The contents ofeach of these applications are hereby incorporated by reference in theirentirety into this disclosure.

BACKGROUND

Atrial fibrillation (“AF”) of the human heart is a common arrhythmiaaffecting millions of people worldwide. Underlying causes includedysfunction of the sinus node, coronary artery disease, andpericarditis. Theoretically, the AF mechanism involves two mainprocesses: (1) higher automaticity in one or more rapidly depolarizingfoci and (2) reentry of conduction involving one or more circuits. Rapidatrial foci, often located in at least one of the superior pulmonaryveins, can begin AF in predisposed patients. In addition, the“multiple-wavelet hypothesis” has been proposed as a potential mechanismfor AF caused by conduction reentry. According to the hypothesis, normalconduction wave fronts break up, resulting in a number ofself-perpetuating “daughter” wavelets that spread through the atriacausing abnormal contraction of the myocardium.

Surgical treatment of AF requires the construction of barriers toconduction within the right atrium and left atrium to restrict theamount of myocardium available to spread reentrant wave fronts, therebyinhibiting sustained AF. By making incisions in the myocardium,conduction is interrupted. Since it has been demonstrated that thepulmonary veins often contain the specific rapidly-depolarizing loci,incisions encircling the pulmonary veins can help prevent AF. Similarly,potentially arrhythmogenic foci close to the pulmonary veins, as well asspecific atrial regions with the shortest refractory periods, may beisolated from the rest of the atria by strategically placed incisions.Although the risk of such surgery alone is typically less than 1%, theneed for median sternotomy and the use of cardiopulmonary bypass, aswell as a risk of short-term fluid retention, make this procedure lessthan ideal.

As an alternative to surgery, catheter ablation has evolved as astandard therapy for patients at high risk for ventricular andsupraventricular tachyarrhythmia. The recognition that foci triggeringAF frequently initiate within the pulmonary veins has led to ablationstrategies that target this zone or that electrically isolate thepulmonary veins from the left atrium. In the superior vena cava, theright atrium, left atrium, and coronary sinus were found as other sitesof arrhythmogenic foci.

In most circumstances, the cardiac ablation catheter is inserted into ablood vessel (artery or vein), usually through an entry site located inthe upper leg or neck. Under fluoroscopy, the tube is navigated throughthe blood vessels until it reaches the heart. In the heart, electrodesat the catheter tip gather data that pinpoint the location of faultytissue in the heart (electrical mapping). Once the site is identified,the device delivers either radiofrequency energy (RF ablation) orintense cold (cryoablation) to destroy the small section of tissue. Themajor goal of this procedure is segmental pulmonary vein isolation andcircumferential pulmonary vein ablation. The circumferential ablationstrategy yields either an atriovenous electrical disconnection, asdemonstrated by elimination of pulmonary vein ostial potentials andabsence of discrete electrical activity inside the lesion during pacingfrom outside the ablation line, or a profound atrial electroanatomicalremodeling as expressed by voltage abatement inside and around theencircled areas involving to some extent the posterior wall of the leftatrium. The endpoint is the electrical isolation of the pulmonary veinsfrom the left atrium, as they house foci triggering AF in about 80% toabout 95% of cases and seem to play a key role in arrhythmiamaintenance.

Possible complications of catheter ablation for AF include systemicembolism, pulmonary vein stenosis, pericardial effusion, cardiactamponade, and phrenic nerve paralysis. The majority of these risks stemfrom the ablation of an incorrect region. Hence, proper navigationduring cardiac ablation is one of the greatest challenges for theelectrophysiologist performing the procedure.

BRIEF SUMMARY

Disclosed herein are systems and methods for navigating a catheter alonga tissue surface, such as the epicardial surface of the heart. Thedisclosed embodiments include, but are not limited to, systems andmethods useful for epicardial ablation. Various embodiments permitablation of the epicardial surface of the heart using an externalablation catheter in the pericardial space and an internal guidecatheter within the heart. Such a configuration allows the clinician toprecisely target for ablation specific locations on the cardiac tissue.

At least some embodiments include a system for navigating a catheter ona surface of a tissue, comprising an external catheter having a distalend and a first magnet positioned at or near the distal end of theexternal catheter; and an internal catheter comprising a distal end anda first magnet positioned at or near the distal end of the internalcatheter; wherein the internal catheter is configured for engaging theexternal catheter when a portion of the external catheter is positionedon or adjacent to a first surface of the tissue and a portion of theinternal catheter is positioned on or adjacent to an opposing surface ofthe tissue, such that manipulation of the internal catheter is capableof directing the external catheter. In at least some embodiments, thefirst surface of the tissue comprises an epicardial surface of a heart,and the opposing surface of the tissue comprises an endocardial surfaceof the heart.

In some embodiments, the external catheter further comprises an ablationcontact positioned at or near the distal end of the external surface,the ablation contact being configured to remove or destroy tissue.

The first magnet of the internal catheter may comprise a first electrodecapable of transitioning between a magnetized state, in which theelectrode attracts the first magnet of the external catheter, and anonmagnetized state, in which the electrode does not significantlyattract the first magnet of the external catheter. The internal cathetermay further comprise a second electrode positioned at or near the distalend of the internal catheter, the second electrode of the internalcatheter being capable of transitioning between a magnetized state, inwhich the electrode attracts the first magnet of the external catheter,and a nonmagnetized state, in which the electrode does not significantlyattract the first magnet of the external catheter.

Some embodiments of internal catheter may further comprise a pair ofexcitation electrodes positioned at or near the distal end of theinternal catheter and a pair of detection electrodes positioned on theinternal catheter between the pair of the excitation electrodes. Aproximal end of each of the pair of excitation electrodes and each ofthe pair of detection electrodes may be connected to a processor, theprocessor being capable of collecting conductance data. The conductancedata may be determined at each of a plurality of locations. Theprocessor may also be capable of determining a profile of a body lumenusing the conductance data.

In at least some embodiments, the conductance data comprises a firstconductance value determined at each of the plurality of locations whenthe excitation electrodes and detection electrodes are immersed in afirst fluid with a first conductivity and a second conductance valuedetermined at each of the plurality of locations when the excitationelectrodes and detection electrodes are immersed in a second fluid witha second conductivity. The first conductivity may not equal the secondconductivity.

In some embodiments, the internal catheter further comprises a thirdelectrode and a fourth electrode, each of which is positioned at or nearthe distal end of the internal catheter and each of which is capable oftransitioning between a magnetized state, in which the electrodeattracts the first magnet of the external catheter, and a nonmagnetizedstate, in which the electrode does not significantly attract the firstmagnet of the external catheter. The internal catheter may be capable offorming a loop within the heart such that the first, second, third, andfourth electrodes are located within the heart. The internal cathetermay further comprise a passageway for passing a fluid through theinternal catheter to the body lumen.

In some embodiments, the first magnet of the external catheter comprisesa first electrode capable of transitioning between a magnetized state,in which the electrode attracts the first magnet of the internalcatheter, and a nonmagnetized state, in which the electrode does notsignificantly attract the first magnet of the internal catheter. Theexternal catheter may further comprise a second magnet positioned at ornear the distal end of the external catheter, including a secondelectrode being capable of transitioning between a magnetized state, inwhich the electrode attracts the first magnet of the internal catheter,and a nonmagnetized state, in which the electrode does not significantlyattract the first magnet of the internal catheter.

Also disclosed herein are embodiments of systems for use with a vacuumsource for ablating a tissue of a heart, comprising an engagementcatheter comprising a proximal end, a distal end, and first and secondlumens extending between the proximal end and the distal end; anexternal catheter comprising a distal end, an ablation contactpositioned at or near the distal end of the external catheter, and afirst magnet positioned at or near the distal end of the externalcatheter, wherein the external catheter is configured such that theexternal catheter is capable of at least partial insertion into thesecond lumen of the engagement catheter; an internal catheter comprisinga distal end and a first magnet positioned at or near the distal end ofthe internal catheter; and a vacuum port located at the proximal end ofthe engagement catheter, the vacuum port being operatively connected tothe first lumen of the engagement catheter and capable of operativeconnection to the vacuum source; wherein the first lumen of theengagement catheter includes a suction port located at or near thedistal end of the engagement catheter, the suction port being configuredto removably attach to a targeted tissue on the interior of a wall ofthe heart, such that the suction port is capable of forming a reversibleseal with the targeted tissue when the vacuum source is operativelyattached to the vacuum port, wherein the internal catheter is configuredfor engaging the external catheter when a portion of the externalcatheter is positioned on or adjacent to an epicardial surface of theheart and a portion of the internal catheter is positioned on oradjacent to an endocardial surface of the heart, such that manipulationof the internal catheter is capable of directing the external catheter,and wherein the system is capable of enlarging a pericardial spacebetween the targeted tissue and a pericardial sac that surrounds theheart by retracting the targeted tissue away from the pericardial sac.

In various embodiments, the internal catheter further comprises a pairof excitation electrodes positioned at or near the distal end of theinternal catheter and a pair of detection electrodes positioned on theinternal catheter between the pair of the excitation electrodes. Aproximal end of each of the pair of excitation electrodes and each ofthe pair of detection electrodes may be connected to a processor, theprocessor being capable of collecting conductance data. The conductancedata may comprise a first conductance value determined at each of aplurality of locations when the excitation electrodes and detectionelectrodes are immersed in a first fluid with a first conductivity and asecond conductance value determined at each of the plurality oflocations when the excitation electrodes and detection electrodes areimmersed in a second fluid with a second conductivity. In at least someembodiments, the first conductivity does not equal the secondconductivity.

Also disclosed herein are methods of navigation and ablation. In someembodiments, a method of ablating a tissue comprises providing anexternal catheter comprising a distal end, a first magnet positioned ator near the distal end of the external catheter, and an ablation contactpositioned at or near the distal end of the external catheter, theablation contact being configured to remove or destroy tissue; providingan internal catheter comprising a distal end and a first magnetpositioned at or near the distal end of the internal catheter, theinternal catheter being configured for engaging the external catheter;placing the distal end of the external catheter adjacent to a firstsurface of the tissue; placing the distal end of the internal catheteradjacent to an opposing surface of the tissue; manipulating the internalcatheter to direct the ablation contact of the external catheter tocontact a first targeted location on the first surface of the tissue;and ablating the first targeted location on the first surface of thetissue. In at least some embodiments, the tissue may comprise cardiactissue, the first surface of the tissue may comprise the epicardialsurface of the cardiac tissue, and the opposing surface of the tissuemay comprise the endocardial surface of the cardiac tissue.

In some embodiments, the step of manipulating the internal catheter todirect the ablation contact of the external catheter to contact a firsttargeted location on the first surface of the tissue comprises (i)engaging the first magnet of the external catheter with the first magnetof the internal catheter such that moving the first magnet of theinternal catheter moves the first magnet of the external catheter, (ii)moving the first magnet of the internal catheter along the endocardialsurface of the cardiac tissue such that the ablation contact of theexternal catheter moves along the epicardial surface of the cardiactissue to the first targeted location on the epicardial surface of thecardiac tissue.

In some embodiments, the step of manipulating the internal catheter todirect the ablation contact of the external catheter to contact a firsttargeted location on the first surface of the tissue may comprise (i)positioning the first electrode of the internal catheter, (ii) switchingthe first electrode of the internal catheter to the magnetized statesuch that the ablation contact of the external catheter is moved to thefirst targeted location on the first surface of the tissue.

In at least some embodiments, the methods further comprise the steps ofmanipulating the internal catheter to direct the ablation contact of theexternal catheter to contact a second targeted location on the firstsurface of the tissue and ablating the second targeted location on thefirst surface of the tissue.

The step of manipulating the internal catheter to direct the ablationcontact of the external catheter to contact a second targeted locationon the first surface of the tissue may further comprise (i) switchingthe first electrode of the internal catheter to the nonmagnetized state,and (ii) switching the second electrode of the internal catheter to themagnetized state such that the ablation contact of the external catheteris moved to the second targeted location on the first surface of thetissue.

In some embodiments, the method further includes ablating the firstsurface of the tissue between the first targeted location on the firstsurface of the tissue and the second targeted location on the firstsurface of the tissue. Moreover, some embodiments include ablating thefirst surface of the tissue in a specified circumference, thecircumference being approximately defined by a loop of the internalcatheter.

The step of manipulating the internal catheter to direct the ablationcontact of the external catheter to contact a first targeted location onthe first surface of the tissue may further comprise (i) measuring afirst conductance value at a first location, (ii) measuring a secondconductance value at a second location, and (iii) determining a profileof a body lumen based on the first conductance value and the secondconductance value.

In at least some embodiments, a method of ablating a targeted tissue onan epicardial surface of a heart may comprise providing an externalcatheter comprising a distal end, a first magnet positioned at or nearthe distal end of the external catheter, and an ablation contactpositioned at or near the distal end of the external catheter, whereinthe ablation contact is configured to remove or destroy tissue;providing an internal catheter comprising a distal end, a firstelectrode positioned at or near the distal end of the internal catheter,and a second electrode positioned at or near the distal end of theinternal catheter; placing the distal end of the internal catheterwithin the heart, such that the first and second electrodes arepositioned within the heart at a desired ablation location and in adesired ablation pattern; activating the first electrode of the internalcatheter such that the ablation contact of the external catheter isdirected to the targeted tissue at a first location; activating theablation contact to ablate the targeted tissue; deactivating the firstelectrode of the internal catheter; and activating the second electrodeof the internal catheter such that the ablation contact of the externalcatheter is directed to the targeted tissue at a second location;wherein the targeted tissue is ablated by the ablation contact betweenthe first location and the second location.

Various embodiments further include the steps of extending into a bloodvessel an elongated tube having a proximal end, a distal end, and afirst lumen, such that the distal end of the tube is in contact with atargeted tissue on the interior of a wall of the heart; aspirating thetargeted tissue on the interior of the wall of the heart such that thewall of the heart is retracted away from a pericardial sac surroundingthe heart to enlarge a pericardial space between the pericardial sac andthe wall of the heart; accessing the pericardial space through thetargeted tissue; and inserting at least the distal end of the externalcatheter into the pericardial space.

Certain embodiments also include the steps of introducing an impedancecatheter into the heart; measuring a first conductance value at a firstlocation in the body; and measuring a second conductance value at asecond location in the body. At least some embodiments further comprisethe step of determining a profile of a body lumen using the conductancedata.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the visual output of an embodiment of a catheter system forlocalization during an experiment of movement through an interior of asurgical glove;

FIG. 2 shows the visual output of an embodiment of a catheter system forlocalization during an experiment of movement through an interior of aheart;

FIG. 3A shows an embodiment of a catheter for localization of a bodylumen juncture;

FIG. 3B shows another embodiment of a catheter for localization of abody lumen juncture;

FIG. 3C shows an embodiment of a catheter for localization and ablationof a body lumen juncture;

FIG. 4A shows another embodiment of a catheter for localization;

FIG. 4B shows an embodiment of a balloon catheter having impedancemeasuring electrodes supported in front of the stenting balloon;

FIG. 4C shows another embodiment of a balloon catheter having impedancemeasuring electrodes within and in front of the balloon;

FIG. 4D shows an embodiment of a catheter having an ultrasoundtransducer within and in front of the balloon;

FIG. 4E shows an embodiment of a guide catheter with wire and impedanceelectrodes;

FIG. 4F shows an embodiment of a catheter with multiple detectionelectrodes;

FIG. 5A shows an embodiment of a catheter in cross-section proximal tothe location of the sensors showing the leads embedded in the materialof the probe;

FIG. 5B shows another embodiment of a catheter in cross-section proximalto the location of the sensors showing the leads run in separate lumens;

FIG. 6 is a schematic of an embodiment of a system showing a cathetercarrying impedance measuring electrodes connected to a data processorequipment and excitation unit for the measurement of conductance and/orcross-sectional area;

FIG. 7A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 1.5% NaCl solution;

FIG. 7B shows the peak-to-peak envelope of the detected voltage shown inFIG. 7A;

FIG. 8A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 0.5% NaCl solution;

FIG. 8B shows the peak-to-peak envelope of the detected voltage shown inFIG. 8A;

FIG. 9 shows balloon distension of the lumen of the coronary artery;

FIG. 10 shows balloon distension of a stent into the lumen of thecoronary artery;

FIG. 11A shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 0.5%NaCl bolus is injected into the treatment site;

FIG. 11B shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 1.5%NaCl bolus is injected into the treatment site;

FIG. 12A shows an embodiment of an engagement catheter and an embodimentof a delivery catheter as disclosed herein;

FIG. 12B shows a percutaneous intravascular pericardial delivery usinganother embodiment of an engagement catheter and another embodiment of adelivery catheter as disclosed herein;

FIG. 13A shows a percutaneous intravascular technique for accessing thepericardial space through a right atrial wall or atrial appendage usingthe engagement and delivery catheters shown in FIG. 12A;

FIG. 13B shows the embodiment of an engagement catheter shown in FIG.2A;

FIG. 13C shows another view of the distal end of the engagement catheterembodiment shown in FIGS. 13A and 13B;

FIG. 14A shows removal of an embodiment of a catheter as disclosedherein;

FIG. 14B shows the resealing of a puncture according to an embodiment asdisclosed herein;

FIG. 15A to 15C show a closure of a hole in the atrial wall using anembodiment as disclosed herein;

FIG. 16A shows an embodiment of an engagement catheter as disclosedherein;

FIG. 16B shows a cross-sectional view of the proximal end of theengagement catheter shown in FIG. 16A;

FIG. 16C shows a cross-sectional view of the distal end of theengagement catheter shown in FIG. 16A;

FIG. 16D shows the engagement catheter shown in FIG. 5A approaching aheart wall from inside of the heart;

FIG. 17A shows an embodiment of a delivery catheter as disclosed herein;

FIG. 17B shows a close-up view of the needle shown in FIG. 6A;

FIG. 17C shows a cross-sectional view of the needle shown in FIGS. 6Aand 6B;

FIG. 18 shows a side view of an embodiment of an external catheter andan embodiment of an internal catheter as disclosed herein;

FIG. 19 shows a perspective view of another embodiment of an externalcatheter and another embodiment of an internal catheter as disclosedherein; and

FIG. 20 shows a close-up view of a distal end of an embodiment of aninternal catheter as disclosed herein.

DETAILED DESCRIPTION

It will be appreciated by those of skill in the art that the followingdetailed description of the disclosed embodiments is merely exemplary innature and is not intended to limit the scope of the appended claims.Indeed, although certain embodiments are described with respect toablation of cardiac tissue, the embodiments disclosed herein may be usedwith respect to any tissue that can be treated by ablation or similarmedical techniques.

The disclosed embodiments include, but are not limited to, systems andmethods useful for epicardial ablation. For example, various embodimentsdisclosed herein permit ablation of the epicardial surface of the heartusing an external ablation catheter in the pericardial space and aninternal guide catheter within the heart. Such a configuration allowsthe clinician to precisely target for ablation specific locations on thecardiac tissue.

Ablation of the epicardial surface of the cardiac tissue is advantageousbecause it requires less penetration of tissue destruction than otherablation methods and is therefore useful in preventing transmuraldamage. This is particularly important for treating ventriculararrhythmias because the ventricular wall is relatively thick. The goalof the ablation is to destroy the arrhythmic cells while preserving thenormal cardiac cells, and success is often dependant on the ability toprecisely ablate in a specific location.

Proper in vivo localization of catheters, the targeted tissue, andcardiac and venous structure during an ablation or similar medicalprocedure can therefore be important for the safety and efficacy of theprocedure. Localization may be made by using the devices, systems, andmethods disclosed in International Patent Application No.PCT/US2007/015239, filed Jun. 29, 2007, the contents of which areincorporated herein by reference. Although localization or visualizationduring intraluminal catheter navigation by the devices, systems, andmethods disclosed herein are advantageous, intraluminal navigation maybe performed by any suitable method.

During various medical procedures involving intraluminal insertion ofcatheters or other devices, proper navigation of the device through bodylumens, such as blood vessels or the heart, is critical to the successof the procedure. Indeed, unless the tissue targeted for treatment ordiagnosis during the procedure is properly located, the procedure can beineffective or, even worse, damaging to nearby healthy tissue.Therefore, a number of the embodiments disclosed herein permit aclinician to readily locate a catheter, such as an ablation catheter, orother medical device within a body lumen in relation to body lumenjunctions or other anatomical structures within the lumen. This leads toproper localization of targeted tissue and increased favorable outcomes.

Some of the disclosed embodiments measure electrical conductance withinthe body lumen and display a profile of relative conductance values,while other embodiments use conductance data to calculate luminalcross-sectional areas and display a profile of relative cross-sectionalareas along a portion of the lumen. These profiles enable the clinicianto readily locate the targeted tissue for further treatment, such asablation. In some embodiments, the conductance catheter and the ablationcatheter is combined into one device so that ablation can occurimmediately following localization, without requiring a change ofcatheters.

Many of the disclosed embodiments do not calculate an absolute value fora lumen's cross-sectional area, but instead measure electricalconductance through a portion of the lumen to form a profile of thelumen. Often, the profile comprises relative conductances taken alongthe lumen. However, because conductance is proportional tocross-sectional area, as explained herein, the profile can compriserelative cross-sectional areas that have been determined from theconductances taken along the lumen.

By monitoring the profile during catheterization, the clinician canvisualize the anatomical structure of the lumen. For example, using apush through or a pull back of a disclosed embodiment of a catheterthrough a lumen, a clinician is able to localize a junction or otherarchitectural marker in the body lumen. Such a push through or pull backwill reflect, in relative terms, the lumen's changes in conductance, andtherefore its changes in cross-sectional area, as the catheter moves,thereby depicting changes in lumen structure across a distance. Based onsuch changes in lumen structure, a clinician can determine the locationsof various anatomical markers of the lumen, as well as the location ofthe catheter in relation to those markers. For example, localization ofthe junction between the relatively small pulmonary veins and thesignificantly larger atrium is possible by assessing the change inconductance (and therefore in cross-sectional area) of the lumen as thecatheter is pushed through the vein into the atrium.

Once a specific lumen junction or other anatomical structure islocalized, the clinician can better treat a targeted tissue at or nearthat identifying structure. Such treatment may include, for example,ablation, localized drug delivery, angioplasty, or stent delivery. Onecommon use of ablation is to electrically isolate arrhythmogenic foci,which are often found in the superior pulmonary veins, from the leftatrium to prevent atrial fibrillation in at-risk patients. To isolatethe vein and prevent further arrhythmogenic conduction from the foci,the cardiac tissue surrounding the pulmonary vein at or adjacent to thepulmonary vein-atrial junction is ablated. Ablation can be performed ina number of ways, including mechanically, electrically, using heat, orusing cryoablation. Regardless of the method for removing or destroyingthe targeted tissue, the clinician preparing to ablate an area ofcardiac tissue surrounding a pulmonary vein must direct the ablationdevice, often a catheter configured for ablation, to the targeted tissuesurrounding the pulmonary vein-atrial junction.

Various devices, systems, and methods for localization of body lumenjunctures disclosed herein permit the clinician to accurately locate thepulmonary vein-atrial junction, as well as confirm the location of theablation catheter with respect to the junction (and, therefore, thetargeted tissue). Indeed, localization using the disclosed embodimentswill minimize undesired ablation into the pulmonary veins, which causesshrinkage of collagen and hence pulmonary vein stenosis. It will alsominimize the ablation of the atrium too far from the pulmonary vein,where the ablation circumference is too large and isolation ofconductance is unlikely.

Experiments have demonstrated the ability of the disclosed embodimentsto provide accurate and reliable feedback as to the location of acatheter within a body lumen. For instance, a surgical glove was filledwith saline to simulate a left atrium (the palm) and pulmonary veins(the fingers). A catheter configured for localization as describedherein was pulled back from inside a finger to the palm, therebysimulating the transition from a pulmonary vein to the atrium. FIG. 1shows the conductance profile 10 as the catheter was pulled back from afinger into the palm of the glove, then was pushed into a finger. As canbe seen, the profile shows that the conductance of the palm wassignificantly larger than the conductance of the finger, and thetransition or demarcation from the finger to the palm is apparent.Because conductance and cross-sectional area are proportional (asdiscussed below), conductance profile 10 is proportional to the CSAprofile (not shown) and distinguishes between the smallercross-sectional area of the fingers and the larger cross-sectional areaof the palm.

A similar pullback experiment was carried out in a heart. Starting fromthe pulmonary vein, a catheter configured for localization as describedherein was pulled back from the pulmonary vein into the left atrium andventricle. FIG. 2 shows a conductance tracing 12 that reflects theconductance for each region of the body lumen as the catheter is pulledback over a distance of about 5 cm from a starting point in thepulmonary vein. The pulmonary vein can be clearly identified byreference to its relative conductance compared to those of the leftatrium, the mitral valve, and the left ventricle. Indeed, the atrial CSAis significantly larger than that of the pulmonary vein, and the atrialCSA increases with distance away from the pulmonary vein-atrialjunction. A reduction in CSA is then observed as the catheter approachesand crosses the mitral valve. Once the catheter progresses through themitral valve into the ventricle, the CSA increases gradually.

Using conductance data like that shown in FIG. 2, a clinician is able tolocate the pulmonary vein-atrial junction, and then the tissue targetedfor ablation, using a localization catheter as disclosed herein. Forinstance, once the end of the pulmonary vein is identified using thetype of conductance data shown in FIG. 2 (i.e., where the conductancebegins to increase), a 2 mm to 3 mm pullback will provide an appropriateregion for ablation in most situations. The axial position of thecatheter can be determined by the velocity of the pullback. The exactamount of necessary pullback should be determined by the clinician on acase by case basis based on the size of the patient and other relevantfactors.

A conductance or impedance catheter measures conductance within a bodylumen using a number of electrodes. Referring now to FIG. 3A, there isshown a conductance catheter 400 configured to localize a body lumenjunction using conductance measurements. Catheter 400 has a proximal end405 and a distal end 410, which is suitable for introduction into a bodylumen. In addition, catheter 400 includes a pair of excitationelectrodes 415 and a pair of detection electrodes 420. Each ofexcitation electrodes 415 and detection electrodes 420 has a proximalend that is capable of attachment to a processing system (not shown) anda distal end that is located on catheter 400 between proximal end 405and distal end 410. The distal ends of detection electrodes 420 arelocated on catheter 400 between the distal ends of excitation electrodes415. Excitation electrodes 415 are configured to emit a measuredelectrical charge into the body lumen, while detection electrodes 420detect the amount of the charge that travels through a fluid within thebody lumen. As explained in more detail below, a processing systemcalculates the change in electrical charge to determine the conductancethrough the lumen at any given location in the lumen.

As shown in FIG. 3A, electrodes 415 and 420 are located at distal end410 of catheter 400. However, the positioning of the electrodes is notlimited to this distal end portion, but may be anywhere on the catheterthat can assist in providing conductance information to the clinician.Furthermore, multiple sets of electrodes (see, e.g., FIG. 4F) may alsobe used to provide additional information used for mapping the interioranatomical structure of an internal organ, vessel, or other body lumen.

Many embodiments disclosed herein, such as the embodiment shown in FIG.3A, have at least two detection electrodes and two excitationelectrodes. However, in the embodiment shown in FIG. 3B, only twoelectrodes are used. Catheter 425 has a proximal end 430 and a distalend 435, as well as a first electrode 440 and a second electrode 445.Each of electrodes 440 and 445 has a proximal end (not shown) and adistal end located on catheter 425 between proximal end 430 and distalend 435. Because catheter 425 has only two electrodes, each electrodemust serve both the excitation function and the detection function. Toenable a single electrode to send and measure the electric charge, adelay must be added to the circuit. Additionally, a bipolar cathetermust be stationary at the time of measurement, requiring the clinicianto obtain a profile by moving the catheter to a desired location,stopping and taking a measurement, and then moving the catheter again.By contrast, tetrapolar catheters may take a continuous conductancemeasurement as the catheter is pulled or pushed through the body lumen,thereby giving a more detailed profile as compared to bipolar catheters.

Although the embodiments shown in FIG. 3A and FIG. 3B are used primarilyfor localization, certain of the disclosed embodiments combine thefunction of localization and ablation into one catheter and therebyimprove the accuracy and safety of the ablation procedure by allowingthe physician to properly identify the targeted tissue for ablationbefore the ablation begins. For example, catheter 450 shown in FIG. 3Cis a conductance catheter that is configured to both localize a bodylumen junction and ablate targeted tissue at or adjacent to thejunction. Catheter 450 has an ablation contact 460 for removing ordestroying a targeted tissue, two excitation electrodes 470, and twodetection electrodes 480, as well as a passageway 490 for passing fluidthrough catheter 450 to the body lumen. Each of excitation electrodes470 and detection electrodes 480 has a proximal end (not shown) forconnection to a processor and a distal end positioned on catheter 450.The distal ends of detection electrodes 480 are positioned on catheter450 between the distal ends of excitation electrodes 470.

Although at least some embodiments can properly measure lumenconductance in the presence of a bodily fluid (such as blood) within thelumen, certain other embodiments may use fluids injected into the bodylumen to properly calculate lumen conductance and/or cross-sectionalarea, as explained herein. Therefore, some embodiments include a channelthrough which fluid is injected into the body lumen. In the embodimentshown in FIG. 3C, infusion passageway 490 is configured to permit suchinjection so that fluid flowing from passageway 490 will flow at leastto the location of the distal ends of excitation electrodes 470 anddetection electrodes 480. Thus, the fluid passing through passageway 490into the lumen will come in contact with the distal ends of excitationelectrodes 470 and detection electrodes 480.

Referring again to FIG. 3C, ablation contact 460 delivers an electriccurrent to a tissue targeted for ablation. The current passes throughablation contact 460, which is in contact with the targeted tissue,entering the targeted tissue and returning to a grounding pad electrode500 that is positioned on the outside of the body. Grounding padelectrode 500 may be held in place using any acceptable means, includingan adhesive safe for contact with human skin. Although ablation contact460 uses electrical current to destroy targeted tissue, other types ofsuitable ablation methods may be used. For instance, other embodimentsdisclosed herein could ablate tissue using very high heat, mechanicalmeans, or cryoablation.

Referring now to FIGS. 4A to 4F, several embodiments of catheters areillustrated. With reference to the embodiment shown in FIG. 4A, there isshown an impedance catheter 22 with four electrodes 25, 26, 27, and 28placed close to distal end 19 of the catheter. Electrodes 25 and 27 areexcitation electrodes, while electrodes 26 and 28 are detectionelectrodes, thereby permitting measurement of conductance (and thereforecalculation of cross-sectional area) during advancement of the catheter,as described in further detail below.

In addition, catheter 22 possesses an optional infusion passageway 35located proximal to excitation electrode 25, as well as optional ports36 for suction of contents of the body lumen or for infusion of fluid.The fluid to inject through passageway 35 or ports 36 can be anybiologically compatible fluid, but, for some circumstances disclosedherein, the conductivity of the fluid is selected to be different fromthat of blood.

In various embodiments, including for example the embodiment shown inFIG. 4A, the catheter contains a channel 31 for insertion of a guidewire to stiffen the flexible catheter during insertion or datarecording. Additionally, channel 31 may be used to inject fluidsolutions of various concentrations (and various conductivities) intothe body lumen of interest. An additional channel 32 may be connected tothe catheter such that the electrical wires connected to the one or moreelectrodes on the catheter are directed through channel 32 and to a dataprocessor, such as data processor system 100 (see FIG. 6), through anadaptor interface 33, such as an impedance module plug or the like, asdescribed in more detail below.

In addition to localization and ablation, some embodiments disclosedherein provide other functionality. FIGS. 4B-4F show a number ofembodiments of conductance catheters having various functions. Forexample, several such embodiments include an angioplasty balloon, inaddition to impedance electrodes (see, e.g., FIG. 4B). Such cathetersmay include electrodes for accurate detection of organ luminalcross-sectional area and ports for pressure gradient measurements.Hence, when using such catheters, it is not necessary to changecatheters during the procedure, as with the current use of intravascularultrasound. In at least one embodiment, the catheter can provide directmeasurement of the non-stenosed area of the lumen, thereby allowing theselection of an appropriately sized stent for implantation.

With reference to the embodiment shown in FIG. 4B, four wires werethreaded through one of the two lumens of catheter 20 (a 4 Fr.catheter). Catheter 20 has a proximal end and a distal end 19, as wellas excitation electrodes 25, 27 and detection electrodes 26, 28 placedat or near distal end 19. Proximal to these electrodes is an angioplastyor stenting balloon 30 capable of being used to treat stenosis. Thedistance between the balloon and the electrodes is usually small, in the0.5 mm to 2 cm range, but can be closer or farther away, depending onthe particular application or treatment involved. The portion ofcatheter 20 within balloon 30 includes an infusion passageway 35 and apressure port 36.

Detection electrodes 26 and 28 are spaced 1 mm apart, while excitationelectrodes 25 and 27 are spaced 4 mm to 5 mm from either side of thedetection electrodes. The excitation and detection electrodes typicallysurround the catheter as ring electrodes, but they may also be pointelectrodes or have other suitable configurations. These electrodes maybe made of any conductive material, such as platinum iridium or amaterial with a carbon-coated surface to avoid fibrin deposits. In atleast one embodiment, the detection electrodes are spaced with 0.5 mm to1 mm between them and with a distance of between 4 mm and 7 mm to theexcitation electrodes on small catheters. On large catheters, for use inlarger vessels and other larger body lumens, the electrode distances maybe larger. The dimensions of the catheter selected for a treatmentdepend on the size of the vessel or other body lumen and are preferablydetermined in part on the results of finite element analysis.

In one approach, dimensions of a catheter to be used for any givenapplication depend on the optimization of the potential field usingfinite element analysis described below. For small organs or inpediatric patients, the diameter of the catheter may be as small as 0.3mm. In large organs, the diameter may be significantly larger dependingon the results of the optimization based on finite element analysis. Theballoon will typically be sized according to the preferred dimension ofthe organ after the distension. The balloon may be made of materialssuitable for the function, such as, for example, polyethylene, latex,polyestherurethane, or combinations thereof. The thickness of theballoon will typically be on the order of a few microns. The catheterwill typically be made of PVC or polyethylene, though other materialsmay be used equally well. The tip of the catheter can be straight,curved, or angled to facilitate insertion into the coronary arteries orother body lumens, such as, for example, the biliary tract.

Referring again to FIG. 4B, catheter 20 may also include severalminiature pressure transducers (not shown) carried by the catheter orpressure ports for determining the pressure gradient proximal to thesite where the conductance is measured. The pressure is preferablymeasured inside the balloon and proximal to, distal to, and at thelocation of the conductance measurement, and locations proximal anddistal thereto, thereby enabling the measurement of pressure recordingsat the site of stenosis and also the measurement of pressure-differencealong or near the stenosis. In one embodiment, shown in FIG. 4B,catheter 20 includes pressure port 90 and pressure port 91 proximal toor at the site of the conductance measurement for evaluation of pressuregradients. As described below with reference to FIGS. 5A, 5B, and 6, inat least one embodiment, the pressure ports are connected by respectiveconduits in catheter 20 to pressure sensors in the data processor system100 (see FIG. 6). Such pressure sensors are well known in the art andinclude, for example, fiber-optic systems, miniature strain gauges, andperfused low-compliance manometry.

In at least one embodiment, a fluid-filled silastic pressure-monitoringcatheter is connected to a pressure transducer. Luminal pressure can bemonitored by a low compliance external pressure transducer coupled tothe infusion channel of the catheter. Pressure transducer calibrationwas carried out by applying 0 and 100 mmHg of pressure by means of ahydrostatic column.

In another embodiment, shown in FIG. 4C, a catheter 39 includes anotherset of excitation electrodes 40, 41 and detection electrodes 42, 43located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon cross-sectional area during angioplasty orstent deployment. These electrodes are in addition to electrodes 25, 26,27, and 28.

In various embodiments, the conductance may be measured using atwo-electrode system (see FIG. 4D). In other embodiments, such asillustrated in FIG. 4F, the conductances at several locations can bemeasured at the same time using an array of five or more electrodes.Here, excitation electrodes 51, 52 are used to generate the currentwhile detection electrodes 53, 54, 55, 56, and 57 are used to detect thecurrent at their respective sites.

In another embodiment, shown in FIG. 4D, catheter 21 has one or moreimaging or recording devices, such as, for example, ultrasoundtransducers 50 for cross-sectional area and wall thickness measurements.As shown, transducers 50 are located near distal end 19 of catheter 21.

With reference to the embodiment shown in FIG. 4E, electrodes 25, 26,27, and 28 are built onto a wire 18, such as, for example, a pressurewire, and inserted through a guide catheter 23, where the infusion of abolus can be made through the lumen of the guide catheter. Adaptorinterface 33 may be used to house and guide the electrical wires(including proximal portions of the excitation and detection electrodes)to a data processor system 100, while a side channel 34 is used toinject various fluids into catheter 23. In yet another embodiment (notillustrated), the catheter includes a sensor for measurement of the flowof fluid in the body lumen.

Referring now to the embodiment shown in FIG. 9, an angioplasty balloon30 is shown distended within a coronary artery 150 for the treatment ofstenosis. As described above with reference to FIG. 4C, a set ofexcitation electrodes 40, 41 and detection electrodes 42, 43 are locatedwithin angioplasty balloon 30. In another embodiment, shown in FIG. 10,angioplasty balloon 30 is used to distend a stent 160 within bloodvessel 150.

Many of the embodiments described herein may be used as part of asystem, which includes suitable connections between the system's variousparts. As described below with reference to FIGS. 5A, 5B, and 6, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the data processor system 100.

FIGS. 5A and 5B illustrate in cross-section two embodiments 20A and 20Bof a catheter such as catheter 20 shown in FIG. 4B. Each embodiment hasa lumen 60 for inflating and deflating the balloon and a lumen 61 forsuction and infusion. The sizes of these lumens can vary. The electrodeleads 70A are embedded in the material of the catheter in the embodimentshown in FIG. 5A, whereas the electrode leads 70B are tunneled through alumen 71 formed within the body of catheter 20B shown in FIG. 5B.

Pressure conduits for perfusion manometry connect pressure ports 90, 91to transducers included in the data processor system 100. As shown inFIG. 5A, pressure conduits 95A may be formed in catheter 20A. In anotherembodiment, shown in FIG. 5B, pressure conduits 95B constituteindividual conduits within a tunnel 96 formed in catheter 20B. In theembodiments described above where miniature pressure transducers arecarried by the catheter, electrical conductors may be substituted forthese pressure conduits.

With reference to FIG. 6, in at least some embodiments, catheter 20connects to a data processor system 100, to a manual or automatic system105 for distension of the balloon, and to a system 106 for infusion offluid or suction of blood or other bodily fluid. The fluid for infusionmay be heated with heating unit 107 to between 37° C. and 39° C. or tobody temperature. The impedance planimetry system typically includes aconstant current unit, amplifiers, and signal conditioners, butvariations are possible. The pressure system typically includesamplifiers and signal conditioners. The system can optionally containsignal conditioning equipment for recording of fluid flow in the bodylumen.

In at least one embodiment, the system is pre-calibrated and a catheteris available in a package. The package also may contain sterile syringeswith fluids to be injected. The syringes are attached to the machine,and after heating of the fluid by the machine and placement of thecatheter in the body lumen of interest, the user presses a button thatinitiates the injection with subsequent computation of the desiredparameters. The CSA, parallel conductance, and/or other relevantmeasures, such as distensibility, tension, etc., will typically appearon the display panel in the PC module 157. The user can then remove thestenosis by distension or by placement of a stent.

If more than one CSA is measured at the same time, the system cancontain a multiplexer unit or a switch between CSA channels. In at leastone embodiment, each CSA measurement or pressure measurement will bethrough separate amplifier units.

In at least one embodiment, the impedance and pressure data are analogsignals which are converted by analog-to-digital converters 153 andtransmitted to a computer 157 for on-line display, on-line analysis, andstorage. In other embodiments, all data handling is done on an entirelyanalog basis.

The processor system includes software programs for analyzing theconductance data. Additional software calculates cross-sectional areasbased on a number of categories of data, as disclosed herein. However,as discussed in more detail below, to calculate for absolutecross-sectional values, certain errors must be reduced or eliminated.The software can be used to reduce the error in CSA values due toconductance of current in the lumen wall and surrounding tissue and todisplay the two-dimensional or three-dimensional geometry of the CSAdistribution along the length of the vessel (and, optionally, along withthe pressure gradient). In one embodiment of the software, a finiteelement approach or a finite difference approach is used to derive theCSA of organ stenosis, taking parameters such as conductivities of thefluid in the lumen and of the lumen wall and surrounding tissue intoconsideration.

In another embodiment, simpler circuits are used. As explained herein,absolute cross-sectional values may be calculated based on two or moreinjections of different NaCl solutions, which varies the conductivity offluid in the lumen. In other embodiments, the software contains the codefor reducing the error in luminal CSA measurement by analyzing signalsduring interventions, such as infusion of a fluid into the lumen or bychanging the amplitude or frequency of the current from the currentamplifier. The software chosen for a particular application may allowfor computation of the CSA with only a small error instantly or withinacceptable time during the medical procedure.

Referring now to FIG. 4A, catheter 22 measures conductance in the bodylumen by detecting the change in voltage between detection electrodes26, 28, as shown by the following equation:

$\begin{matrix}{{\Delta\; V} = \frac{I \cdot L}{C \cdot {CSA}}} & \left\lbrack {1\; a} \right\rbrack\end{matrix}$

Thus, the change in voltage, ΔV, is equal to the magnitude of thecurrent, I, multiplied by the distance between the detection electrodes,L, divided by the conductivity of the fluid in the lumen, C, and dividedby the cross-sectional area, CSA. Because the current (I), the distance(L), and the conductivity (C) normally can be regarded as calibrationconstants during a localization procedure, an inversely proportionalrelationship exists between the voltage difference and the CSA, as shownby the following equation:

$\begin{matrix}{{\Delta\; V} = \frac{1}{CSA}} & \left\lbrack {1\; b} \right\rbrack\end{matrix}$

In other words, as the cross-sectional area of the lumen decreases, thechange in voltage measured by catheter 22 increases. As discussedearlier, conductance and cross-sectional area are proportional. Thus,this equation permits the relative conductances or cross-sectional areasof various intralumen anatomical structures to be determined frommeasurement of the change in voltage across the lumen using at least oneexcitation electrode and one detection electrode.

This measurement, however, does not produce accurate, or absolute,values of conductance or cross-sectional area because of the loss ofcurrent in the wall of the lumen and surrounding tissue. Althoughrelying on the relative conductances or cross-sectional areas issufficient for the localization of intraluminal structures, otherembodiments for other purposes may require the accurate determination ofabsolute values for cross-sectional areas.

For example, accurate measures of the luminal cross-sectional area oforgan stenosis within acceptable limits enables accurate and scientificstent sizing and placement. Proper stent implantation improves clinicaloutcomes by avoiding under or over deployment and under or over sizingof a stent, which can cause acute closure or in-stent re-stenosis. In atleast one embodiment disclosed herein, an angioplasty or stent balloonincludes impedance electrodes supported by the catheter in front of theballoon. These electrodes enable the immediate determination of thecross-sectional area of the vessel during the balloon advancement. Thisprovides a direct measurement of non-stenosed area and allows theselection of the appropriate stent size. In one approach, error due tothe loss of current in the wall of the organ and surrounding tissue iscorrected by injection of two solutions of NaCl or other solutions withknown conductivities. In another embodiment, impedance electrodes arelocated in the center of the balloon in order to deploy the stent to thedesired cross-sectional area. These embodiments and proceduressubstantially improve the accuracy of stenting and the outcome of suchstenting, as well as reduce overall costs.

Other embodiments make diagnosis of valve stenosis more accurate andmore scientific by providing a direct, accurate measurement ofcross-sectional area of the valve annulus, independent of the flowconditions through the valve. Thus, in such embodiments, the excitationand detection electrodes are embedded within a catheter to measure thevalve area directly, independent of cardiac output or pressure drop, andtherefore errors in the measurement of valve area are minimized.Further, pressure sensors may be mounted proximal and distal to theimpedance electrodes to provide simultaneous pressure gradientrecording.

Other embodiments improve evaluation of cross-sectional area and flow inorgans like the gastrointestinal tract and the urinary tract

At least some of the disclosed embodiments overcome the problemsassociated with determination of the size (cross-sectional area) ofluminal organs, such as, for example, in the coronary arteries, carotid,femoral, renal and iliac arteries, aorta, gastrointestinal tract,urethra, and ureter. In addition, at least some embodiments also providemethods for registration of acute changes in wall conductance, such as,for example, due to edema or acute damage to the tissue, and fordetection of muscle spasms/contractions.

The operation of catheter 20, shown in FIG. 4B, is as follows: forelectrodes 25, 26, 27, 28, conductance of current flow through the organlumen and organ wall and surrounding tissue is parallel; i.e.,

$\begin{matrix}{{G\left( {z,t} \right)} = {\frac{{{CSA}\left( {z,t} \right)} \cdot C_{b}}{L} + {G_{p}\left( {z,t} \right)}}} & \left\lbrack {2\; a} \right\rbrack\end{matrix}$where G_(p)(z,t) is the effective conductance of the structure outsidethe bodily fluid (organ wall and surrounding tissue); C_(b) is thespecific electrical conductivity of the bodily fluid, which for bloodgenerally depends on the temperature, hematocrit, and orientation anddeformation of blood cells; and L is the distance between the detectionelectrodes. This equation shows that conductance, G(z,t), isproportional to the cross-sectional area, CSA (z,t). Thus, a largerconductance will reflect a larger cross-sectional area, and vice versa.

Equation [2a] can be rearranged to solve for cross-sectional areaCSA(z,t), with a correction factor, α, if the electric field isnon-homogeneous, as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {\frac{L}{\alpha\; C_{b}}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \left\lbrack {2\; b} \right\rbrack\end{matrix}$where α would be equal to 1 if the field were completely homogeneous.The parallel conductance, G_(p), is an offset error that results fromcurrent leakage. G_(p) would equal 0 if all of the current were confinedto the blood and hence would correspond to the cylindrical model givenby Equation [1a]. In one approach, finite element analysis is used toproperly design the spacing between detection and excitation electrodesrelative to the dimensions of the body lumen to provide a nearlyhomogenous field such that α can be considered equal to 1. Simulationsshow that a homogenous or substantially homogenous field is provided by(1) the placement of detection electrodes substantially equidistant fromthe excitation electrodes and (2) maintaining the distance between thedetection and excitation electrodes substantially comparable to the bodylumen diameter. In one approach, a homogeneous field is achieved bytaking steps (1) and/or (2) described above so that α equals 1 in theforegoing analysis.

G_(p) is a constant at any given position, z, along the long axis of abody lumen, and at any given time, t, in the cardiac cycle. Hence, twoinjections of different concentrations (and therefore conductivities) ofNaCl solution give rise to two equations:C ₁ ·CSA(z,t)+L·G _(p)(z,t)=L·G ₁(z,t)  [3]C ₂ ·CSA(z,t)+L·G _(p)(z,t)=L·G ₂(Z,t)  [4]which can be solved simultaneously for CSA and G_(p) as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {L\frac{\left\lbrack {{G_{2}\left( {z,t} \right)} - {G_{1}\left( {z,t} \right)}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}}} & \lbrack 5\rbrack \\{{G_{p}\left( {z,t} \right)} = \frac{\left\lbrack {{C_{2} \cdot {G_{1}\left( {z,t} \right)}} - {C_{1} \cdot {G_{2}\left( {z,t} \right)}}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}} & \lbrack 6\rbrack\end{matrix}$where subscript “1” and subscript “2” designate any two injections ofdifferent NaCl concentrations (and conductivities). For each injectionk, C_(k) gives rise to G_(k) which is measured as the ratio of the rootmean square of the current divided by the root mean square of thevoltage. The C_(k) is typically determined through in vitro calibrationfor the various NaCl concentrations. The concentration of NaCl used istypically on the order of 0.45% to 1.8%. The volume of NaCl solution istypically about 5 ml, but the amount of solution should be sufficient tomomentarily displace the entire local vascular blood volume or otherbody lumen fluid. The values of CSA(t) and G_(p)(t) can be determined atend-diastole or end-systole (i.e., the minimum and maximum values) orthe mean thereof. The value of CSA would vary through the cardiac cycle,but G_(p)(t) does not vary significantly.

Once the CSA and G_(p) of the body lumen are determined according to theabove embodiment, rearrangement of Equation [2a] allows the calculationof the specific electrical conductivity of bodily fluid in the presenceof fluid flow as

$\begin{matrix}{C_{b} = {\frac{L}{{CSA}\left( {z,t} \right)}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right.}} & \lbrack 7\rbrack\end{matrix}$

In this way, Equation [2b] can be used to calculate the CSA continuously(temporal variation, as for example through the cardiac cycle) in thepresence of bodily fluid.

In one approach, a pull or push through is used to reconstruct the bodylumen CSA along its length. During a long injection of solution (e.g.,10 s to 15 s), the catheter can be pulled back or pushed forward atconstant velocity U. Equation [2a] can be expressed as

$\begin{matrix}{{{CSA}\left( {{U \cdot t},t} \right)} = {\frac{L}{C_{b}}\left\lbrack {{G\left( {{U \cdot t},t} \right)} - {G_{p}\left( {{U \cdot t},t} \right)}} \right\rbrack}} & \lbrack 8\rbrack\end{matrix}$where the axial position, z, is the product of catheter velocity, U, andtime, t; i.e., z=U·t.

For the two injections, denoted by subscript “1” and subscript “2”,respectively, different time points T₁, T₂, etc. may be considered suchthat Equation [8] can be written as

$\begin{matrix}{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {9\; a} \right\rbrack \\{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {9\; b} \right\rbrack \\{and} & \; \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {10\; a} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {10\; b} \right\rbrack\end{matrix}$and so on. Each set of Equations [9a], [9b] and [10a], [10b], etc., canbe solved for CSA₁, G_(p1) and CSA₂, G_(p2), respectively. Hence, onecan measure the CSA at various time intervals and therefore at differentpositions along the body lumen to reconstruct the length of the lumen.In at least one embodiment, the data on the CSA and parallel conductanceas a function of longitudinal position along the body lumen can beexported from an electronic spreadsheet, such as, for example, aMicrosoft Excel file, to diagramming software, such as AutoCAD®, wherethe software uses the coordinates to render a three-dimensionaldepiction of the lumen on the monitor.

For example, in one approach, the pull back reconstruction was madeduring a long injection where the catheter was pulled back at constantrate by hand. The catheter was marked along its length such that thepull back was made at 2 mm/sec. Hence, during a 10-second injection, thecatheter was pulled back about 2 cm. The data was continuously measuredand analyzed at every two second interval; i.e., at every 4 mm. Thus,six different measurements of CSA and G_(p) were taken which were usedto reconstruct the CSA and G_(p) along the length of the 2 cm segment.

In one approach, the wall thickness is determined from the parallelconductance for those body lumens that are surrounded by air ornon-conducting tissue. In such cases, the parallel conductance is equalto

$\begin{matrix}{G_{p} = \frac{{CSA}_{w} \cdot C_{w}}{L}} & \left\lbrack {11\; a} \right\rbrack\end{matrix}$where CSA_(w) is the CSA of the lumen wall and C_(w) is the electricalconductivity of the wall. This equation can be solved for CSA_(w) as

$\begin{matrix}{{CSA}_{w} = \frac{G_{p} \cdot L}{C_{w}}} & \left\lbrack {11\; b} \right\rbrack\end{matrix}$For a cylindrical body lumen, the wall thickness, h, can be expressed as

$\begin{matrix}{h = \frac{{CSA}_{w}}{\pi\; D}} & \lbrack 12\rbrack\end{matrix}$where D is the diameter of the lumen, which can be determined from thecircular CSA(D=[4CSA/π]^(1/2)).

When the CSA, pressure, wall thickness, and flow data are determinedaccording to the embodiments outlined above, it is possible to computethe compliance (e.g., ΔCSA/ΔAP), tension (e.g., P*r, where P and r arethe intraluminal pressure and radius of a cylindrical lumen), stress(e.g., P*r/h, where h is the wall thickness of the cylindrical organ),strain (e.g., (C-C_(d))/C_(d) where C is the inner circumference andC_(d) is the circumference in diastole), and wall shear stress (e.g., 4μQ/r³ where μ, Q, and r are the fluid viscosity, flow rate, and radiusof the cylindrical lumen for a fully developed flow). These quantitiescan be used in assessing the mechanical characteristics of the system inhealth and disease.

In at least one approach for localization or measuring the conductance(and determining the cross-sectional area) of a body lumen, a catheteris introduced from an exteriorly accessible opening (for example, themouth, nose, or anus for GI applications, or the mouth or nose forairway applications) into the targeted body lumen. For cardiovascularapplications, the catheter can be inserted into the lumens in variousways, such as, for example, those used in conventional angioplasty. Inat least one embodiment, an 18 gauge needle is inserted into the femoralartery followed by an introducer. A guide wire is then inserted into theintroducer and advanced into the lumen of the femoral artery. A 4 or 5Fr. conductance catheter is then inserted into the femoral artery viawire, and the wire is subsequently retracted. The catheter tipcontaining the conductance electrodes can then be advanced to the regionof interest by use of x-ray (e.g., fluoroscopy). In another approach,this methodology is used on small to medium size vessels (e.g., femoral,coronary, carotid, iliac arteries).

In one approach, a minimum of two injections with differentconcentrations of NaCl (and, therefore, different conductivities) arerequired to solve for the two unknowns, CSA and G_(p). However, in otherembodiments disclosed herein, only relative values for conductance orcross-sectional area are necessary, so the injection of two solutions isnot necessary. In another approach, three injections will yield threesets of values for CSA and G_(p) (although not necessarily linearlyindependent), while four injections would yield six sets of values. Inone approach, at least two solutions (e.g., 0.5% and 1.5% NaClsolutions) are injected in the targeted vessel or other lumen. Studiesindicate that an infusion rate of approximately 1 ml/s for a five secondinterval is sufficient to displace the blood volume and results in alocal pressure increase of less than 10 mmHg in the coronary artery.This pressure change depends on the injection rate which should becomparable to the lumen flow rate.

In at least one approach, involving the application of Equations [5] and[6], the vessel is under identical or very similar conditions during thetwo injections. Hence, some variables, such as the infusion rate, bolustemperature, etc., are similar for the two injections. Typically, ashort time interval is to be allowed (1 to 2 minute period) between thetwo injections to permit the vessel to return to homeostatic state. Thiscan be determined from the baseline conductance as shown in FIG. 7A, 7B,8A, or 8B. The parallel conductance is preferably the same or verysimilar during the two injections. Dextran, albumin, or another largemolecular weight molecule may be added to the NaCl solutions to maintainthe colloid osmotic pressure of the solution to reduce or prevent fluidor ion exchange through the vessel wall.

In one approach, the NaCl solution is heated to body temperature priorto injection since the conductivity of current is temperature dependent.In another approach, the injected bolus is at room temperature, but atemperature correction is made since the conductivity is related totemperature in a linear fashion.

In one approach, a sheath is inserted through either the femoral arteryor the carotid artery in the direction of flow. To access the loweranterior descending (“LAD”) artery, the sheath is inserted through theascending aorta. For the carotid artery, where the diameter is typicallyon the order of 5 mm to 5.5 mm, a catheter having a diameter of 1.9 mmcan be used, as determined from finite element analysis, discussedfurther below. For the femoral and coronary arteries, where the diameteris typically in the range from 3.5 mm to 4 mm, so a catheter of about0.8 mm diameter would be appropriate. The catheter can be inserted intothe femoral, carotid, or LAD artery through a sheath appropriate for theparticular treatment. Measurements for all three vessels can be madesimilarly.

Described here are the protocol and results for one approach that isgenerally applicable to most arterial vessels. The conductance catheterwas inserted through the sheath for a particular vessel of interest. Abaseline reading of voltage was continuously recorded. Two containerscontaining 0.5% and 1.5% NaCl were placed in temperature bath andmaintained at 37° C. A 5 ml to 10 ml injection of 1.5% NaCl was madeover a 5 second interval. The detection voltage was continuouslyrecorded over a 10 second interval during the 5 second injection.Several minutes later, a similar volume of 1.5% NaCl solution wasinjected at a similar rate. The data was again recorded. Matlab® wasused to analyze the data including filtering with high pass and with lowcut off frequency (1200 Hz). The data was displayed using Matlab®, andthe mean of the voltage signal during the passage of each respectivesolution was recorded. The corresponding currents were also measured toyield the conductance (G=I/V). The conductivity of each solution wascalibrated with six different tubes of known CSA at body temperature. Amodel using Equation [1a] was fitted to the data to calculateconductivity C. The analysis was carried out with SPSS statisticalsoftware using the non-linear regression fit. Given C and G for each ofthe two injections, an Excel spreadsheet file was formatted to calculatethe CSA and G_(p) as per equations [5] and [6], respectively. Thesemeasurements were repeated several times to determine thereproducibility of the technique. The reproducibility of the data waswithin 5%. Ultrasound was used to measure the diameter of the vesselsimultaneous with our conductance measurements. The detection electrodeswere visualized with ultrasound, and the diameter measurements was madeat the center of the detection electrodes. The maximum differencesbetween the conductance and ultrasound measurements were within 10%.

FIGS. 7A, 7B, 8A, and 8B illustrate voltage measurements in the bloodstream in the left carotid artery. Here, the data acquisition had asampling frequency of 75 KHz, with two channels—the current injected andthe detected voltage, respectively. The current injected has a frequencyof 5 KHz, so the voltage detected, modulated in amplitude by theimpedance changing through the bolus injection, will have a spectrum inthe vicinity of 5 KHz.

With reference to FIG. 7A there is shown a signal processed with a highpass filter with low cut off frequency (1200 Hz). The top and bottomportions 200, 202 show the peak-to-peak envelope detected voltage whichis displayed in FIG. 7B. The initial 7 seconds correspond to thebaseline; i.e., electrodes in the blood stream. The next 7 secondscorrespond to an injection of hyper-osmotic NaCl solution (1.5% NaCl).It can be seen that the voltage is decreased, implying increasedconductance (since the injected current is constant). Once the NaClsolution is washed out, the baseline is recovered as shown in FIGS. 7Aand 7B. FIGS. 8A and 8B show similar data corresponding to 0.5% NaClsolutions.

The voltage signals are ideal since the difference between the baselineand the injected solution is apparent and systematic. Furthermore, thepulsation of vessel diameter can be seen in the 0.5% and 1.5% NaClinjections (FIGS. 7A, 7B and 8A, 8B, respectively). This allowsdetermination of the variation of CSA throughout the cardiac cycle asoutline above.

The NaCl solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the lumen segment of interest. For example, in a blood vessel,the pressure generated by the injection will not only displace the bloodin the antegrade direction (in the direction of blood flow) but also inthe retrograde direction (by momentarily pushing the blood backwards).In other visceral organs which may be normally collapsed, the NaClsolution will not displace blood as in the vessels but will merely openthe organs and create a flow of the fluid. In one approach, afterinjection of a first solution into the treatment or measurement site,sensors monitor and confirm baseline of conductance prior to injectionof a second solution into the treatment site.

The injections described above are preferably repeated at least once toreduce errors associated with the administration of the injections, suchas, for example, where the injection does not completely displace theblood or where there is significant mixing with blood. It will beunderstood that any bifurcation(s) (with branching angle near 90degrees) near the targeted lumen can cause an overestimation of thecalculated CSA. Hence, generally the catheter should be slightlyretracted or advanced and the measurement repeated. An additionalapplication with multiple detection electrodes or a pull back or pushforward during injection will accomplish the same goal. Here, an arrayof detection electrodes can be used to minimize or eliminate errors thatwould result from bifurcations or branching in the measurement ortreatment site.

In one approach, error due to the eccentric position of the electrode orother imaging device can be reduced by inflation of a balloon on thecatheter. The inflation of the balloon during measurement will place theelectrodes or other imaging device in the center of the vessel away fromthe wall. In the case of impedance electrodes, the inflation of theballoon can be synchronized with the injection of a bolus such that theballoon inflation would immediately precede the bolus injection. Ourresults, however, show that the error due to catheter eccentricity issmall.

The CSA predicted by Equation [5] corresponds to the area of the vesselor other lumen external to the catheter (i.e., CSA of vessel minus CSAof catheter). If the conductivity of the NaCl solutions is determined bycalibration from Equation [1a] with various tubes of known CSA, then thecalibration accounts for the dimension of the catheter and thecalculated CSA corresponds to that of the total vessel lumen. In atleast one embodiment, the calibration of the CSA measurement system willbe performed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 mm in diameter). If the conductivity of the solutions isobtained from a conductivity meter independent of the catheter, however,then the CSA of the catheter is generally added to the CSA computed fromEquation [5] to give the total CSA of the vessel.

The signals are generally non-stationary, nonlinear, and stochastic. Todeal with non-stationary stochastic functions, one can use a number ofmethods, such as the Spectrogram, the Wavelet's analysis, theWigner-Ville distribution, the Evolutionary Spectrum, Modal analysis, orthe intrinsic model function (“IMF”) method. The mean or peak-to-peakvalues can be systematically determined by the aforementioned signalanalysis and used in Equation [5] to compute the CSA.

For the determination of conductance or cross-sectional area of a heartvalve, it is generally not feasible to displace the entire volume of theheart. Hence, the conductivity of the blood is transiently changed byinjection of a hypertonic NaCl solution into the pulmonary artery. Ifthe measured total conductance is plotted versus blood conductivity on agraph, the extrapolated conductance at zero conductivity corresponds tothe parallel conductance. In order to ensure that the two innerelectrodes are positioned in the plane of the valve annulus (2 mm to 3mm), in one embodiment, two pressure sensors 36 are placed immediatelyproximal and distal to (1 mm to 2 mm above and below, respectively) thedetection electrodes or sets of detection electrodes (see, e.g., FIGS.4A and 4F). The pressure readings will then indicate the position of thedetection electrode relative to the desired site of measurement (aorticvalve: aortic-ventricular pressure; mitral valve: leftventricular-atrial pressure; tricuspid valve: right atrial-ventricularpressure; pulmonary valve: right ventricular-pulmonary pressure). Theparallel conductance at the site of annulus is generally expected to besmall since the annulus consists primarily of collagen, which has lowelectrical conductivity. In another application, a pull back or pushforward through the heart chamber will show different conductance due tothe change in geometry and parallel conductance. This can be establishedfor normal patients, which can then be used to diagnose valvularstenosis.

In one approach, for the esophagus or the urethra, the procedures canconveniently be done by swallowing fluids of known conductivities intothe esophagus and infusion of fluids of known conductances into theurinary bladder followed by voiding the volume. In another approach,fluids can be swallowed or urine voided followed by measurement of thefluid conductivities from samples of the fluid. The latter method can beapplied to the ureter where a catheter can be advanced up into theureter and fluids can be injected from a proximal port on the probe(will also be applicable in the intestines) or urine production can beincreased and samples taken distal in the ureter during passage of thebolus or from the urinary bladder.

In one approach, concomitant with measuring the conductance,cross-sectional area, and/or pressure gradient at the treatment ormeasurement site, a mechanical stimulus is introduced by way ofinflating the balloon or by releasing a stent from the catheter, therebyfacilitating flow through the stenosed part of the lumen. In anotherapproach, concomitant with measuring the conductance, cross-sectionalarea, and/or pressure gradient at the treatment site, one or morepharmaceutical substances for diagnosis or treatment of stenosis isinjected into the treatment site. For example, in one approach, theinjected substance can be a smooth muscle agonist or antagonist. In yetanother approach, concomitant with measuring the conductance,cross-sectional area, and/or pressure gradient at the treatment site, aninflating fluid is released into the treatment site for release of anystenosis or materials causing stenosis in the lumen or treatment site.

Again, it will be noted that the methods, systems, and cathetersdescribed herein can be applied to any body lumen or treatment site. Forexample, the methods, systems, and catheters described herein can beapplied to any one of the following hollow bodily systems: thecardiovascular system including the heart; the digestive system; therespiratory system; the reproductive system; and the urogenital tract.

Finite Element Analysis: In one preferred approach, finite elementanalysis (FEA) is used to verify the validity of Equations [5] and [6].There are two major considerations for the model definition: geometryand electrical properties. The general equation governing the electricscalar potential distribution, V, is given by Poisson's equation as:∇·(C∇V)=−1  [13]where C, I and ∇ are the conductivity, the driving current density, andthe del operator, respectively. Femlab or any standard finite elementpackage can be used to compute the nodal voltages using Equation [13].Once V has been determined, the electric field can be obtained fromE=−∇V.

The FEA allows the determination of the nature of the field and itsalteration in response to different electrode distances, distancesbetween driving electrodes, wall thicknesses, and wall conductivities.The percentage of total current in the lumen of the vessel (% I) can beused as an index of both leakage and field homogeneity. Hence, thevarious geometric and electrical material properties can be varied toobtain the optimum design, i.e., minimizing the non-homogeneity of thefield. Furthermore, the experimental procedure was simulated byinjection of the two solutions of NaCl to verify the accuracy ofEquation [5]. Finally, the effect of the presence of electrodes and thecatheter in the lumen of vessel was assessed. The error termsrepresenting the changes in measured conductance due to the attractionof the field to the electrodes and the repulsion of the field from theresistive catheter body were quantified.

Poisson's equation was solved for the potential field, which takes intoaccount the magnitude of the applied current, the location of thecurrent driving and detection electrodes, and the conductivities andgeometrical shapes in the model including the vessel wall andsurrounding tissue. This analysis suggests that the following conditionsare optimal for the cylindrical model: (1) the placement of detection(voltage sensing) electrodes equidistant from the excitation (currentdriving) electrodes; (2) the distance between the excitation electrodesshould be much greater than the distance between the detectionelectrodes; and (3) the distance between the detection and excitationelectrodes is comparable to the vessel diameter, or the diameter of thevessel is small relative to the distance between the driving electrodes.If these conditions are satisfied, the equipotential contours moreclosely resemble straight lines perpendicular to the axis of thecatheter and the voltage drop measured at the wall will be nearlyidentical to that at the center. Since the curvature of theequipotential contours is inversely related to the homogeneity of theelectric field, it is possible to optimize the design to minimize thecurvature of the field lines. Consequently, in one approach, one or moreof conditions (1)-(3) described above are met to increase the accuracyof the cylindrical model.

Theoretically, it is impossible to ensure a completely homogeneous fieldgiven the current leakage through the lumen wall into the surroundingtissue. It was found that the iso-potential line is not constant as onemoves out radially along the vessel as stipulated by the cylindricalmodel. FIGS. 11A and 11B show the detected voltage for a catheter with aradius of 0.55 mm for two different NaCl solutions (0.5% and 1.5%,respectively). The origin corresponds to the center of the catheter. Thefirst vertical line 220 represents the inner part of the electrode whichis wrapped around the catheter, and the second vertical line 221 is theouter part of the electrode in contact with the solution (diameter ofelectrode is approximately 0.25 mm). The six different curves, top tobottom, correspond to six different vessels with radii of 3.1 mm, 2.7mm, 2.3 mm, 1.9 mm, 1.5 mm, and 0.55 mm, respectively. It can be seenthat a “hill” 220, 221 occurs at the detection electrodes, followed by afairly uniform plateau in the vessel lumen, followed by an exponentialdecay into the surrounding tissue. Since the potential difference ismeasured at the detection electrode 220, 221, the simulation generatesthe “hill” whose value corresponds to the equivalent potential in thevessel as used in Equation [5]. Thus, for each catheter size, thedimension of the vessel was varied such that Equation [5] was exactlysatisfied. Consequently, the optimum catheter size for a given vesseldiameter was obtained such that the distributive model satisfies thelumped equations (Equations [5] and [6]). In this way, a relationshipbetween vessel diameter and catheter diameter can be generated such thatthe error in the CSA determination is less than 5%. In one embodiment,different diameter catheters are prepackaged and labeled for optimal usein certain size vessel. For example, for vessel dimensions in the rangeof 4 mm to 5 mm, 5 mm to 7 mm, or 7 mm to 10 mm, analysis shows thatoptimum diameter catheters will be in the range of 0.9 mm to 1.4 mm, 1.4mm to 2 mm, or 2 mm to 4.6 mm, respectively. The clinician can selectthe appropriate diameter catheter based on the estimated vessel diameterof interest. This decision will be made prior to the procedure and willserve to minimize the error in the determination of lumen CSA.

Thus, a number of the embodiments disclosed herein accurately calculatelumen cross-sectional area by measuring conductance and correcting forvarious errors inherent in such measurements. However, at least some ofthe disclosed embodiments provide for the localization of body lumenjunctions and other intraluminal anatomical structures using relativeconductances and/or cross-sectional areas. Because only relativedifferences in conductance or cross-sectional area are necessary foraccurate localization, the calculation of absolute values for variouslocations within the body lumen may be skipped in most instances.

Percutaneous access to the pericardial space may be obtained usingdevices and methods disclosed in International Patent Application No.PCT/US2007/015207, filed Jun. 29, 2007, the contents of which areincorporated herein by reference. Although navigation to the pericardialspace from the intravascular region (inside of the heart) provides morecertainty of position of vital cardiac structures than doesintrathoracic access (from outside of the heart), access to thepericardial space may be obtained by any suitable method.

In the embodiment of the catheter system shown in FIG. 12A, cathetersystem 250 includes an engagement catheter 254, a delivery catheter 256,and a needle 260. Although each of engagement catheter 254, deliverycatheter 256, and needle 260 has a proximal end and a distal end, FIG.12A shows only the distal end. Engagement catheter 254 has a lumenthrough which delivery catheter 256 has been inserted, and deliverycatheter 256 has a lumen through which needle 260 has been inserted.Delivery catheter 256 also has a number of openings 264 that can be usedto transmit fluid from the lumen of the catheter to the heart tissue inclose proximity to the distal end of the catheter.

As shown in more detail in FIGS. 13A, 13B, 13C, engagement catheter 254includes a vacuum channel 266 used for suction of a targeted tissue 268in the heart and an injection channel 270 used for infusion ofsubstances to targeted tissue 268, including, for example, a biologicalor non-biological degradable adhesive. As is shown in FIGS. 13B and 13C,injection channel 270 is ring-shaped, which tends to provide relativelyeven dispersal of the infused substance over the targeted tissue, butother shapes of injection channels may be suitable. A syringe 272 isattached to injection channel 270 for delivery of the appropriatesubstances to injection channel 270, and a syringe 274 is attached tovacuum channel 266 through a vacuum port (not shown) at the proximal endof engagement catheter 254 to provide appropriate suction through vacuumchannel 266. At the distal end of engagement catheter 254, a suctionport 278 is attached to vacuum channel 266 for contacting targetedtissue 268, such that suction port 278 surrounds targeted tissue 268,which is thereby encompassed within the circumference of suction port278. Although syringe 274 is shown in FIG. 13B as the vacuum sourceproviding suction for engagement catheter 254, other types of vacuumsources may be used, such as a controlled vacuum system providingspecific suction pressures. Similarly, syringe 272 serves as theexternal fluid source in the embodiment shown in FIG. 13B, but otherexternal fluid sources may be used.

A route of entry for use of various embodiments disclosed herein isthrough the jugular or femoral vein to the superior or inferior venacavae, respectively, to the right atrial wall or atrial appendage(percutaneously) to the pericardial sac (through puncture).

Referring now to FIG. 12B, an engagement catheter 280 is placed viastandard approach into the jugular or femoral vein. The catheter, whichmay be 4 or 5 Fr., is positioned under fluoroscopic or echocardiographicguidance into the right atrial appendage 282. Suction is initiated toaspirate a portion of atrial appendage 282 away from the pericardial sac286 that surrounds the heart. As explained herein, aspiration of theheart tissue is evidenced when no blood can be pulled back throughengagement catheter 280 and, if suction pressure is being measured, whenthe suction pressure gradually increases. A delivery catheter 290 isthen inserted through a lumen of engagement catheter 280. A smallperforation can be made in the aspirated atrial appendage 282 with aneedle such as needle 260, as shown in FIGS. 12A and 13A. A guide wire(not shown) can then be advanced through delivery catheter 290 into thepericardial space to secure the point of entry 292 through the atrialappendage and guide further insertion of delivery catheter 290 oranother catheter. Fluoroscopy or echocardiogram can be used to confirmthe position of the catheter in the pericardial space. Alternatively, apressure tip needle can sense the pressure and measure the pressurechange from the atrium (about 10 mmHg) to the pericardial space (about 2mmHg). This is particularly helpful for transeptal access where punctureof arterial structures (e.g., the aorta) can be diagnosed and sealedwith an adhesive, as described in more detail below.

Although aspiration of the atrial wall or the atrial appendage retractsthe wall or appendage from the pericardial sac to create additionalpericardial space, CO₂ gas can be delivered through a catheter, such asdelivery catheter 290, into the pericardial space to create additionalspace between the pericardial sac and the heart surface.

Referring now to FIG. 14A, the catheter system shown in FIG. 12B isretrieved by pull back through the route of entry. However, the punctureof the targeted tissue in the heart (e.g., the right atrial appendage asshown in FIG. 14A) may be sealed upon withdrawal of the catheter, whichprevents bleeding into the pericardial space. The retrieval of thecatheter may be combined with a sealing of the tissue in one of severalways: (1) release of a tissue adhesive or polymer 296 via injectionchannel 270 to seal off the puncture hole, as shown in FIG. 14B; (2)release of an inner clip or mechanical stitch to close off the hole fromthe inside of the cavity; or (3) mechanical closure of the heart with asandwich type mechanical device that approaches the hole from both sidesof the wall (see FIGS. 15A, 15B, and 15C). In other words, closure maybe accomplished by using, for example, a biodegradable adhesive material(e.g., fibrin glue or cyanomethacrylate), a magnetic system, or anumbrella-shaped nitinol stent. An example of the closure of a hole inthe atrium is shown in FIG. 3B. Engagement catheter 254 is attached totargeted tissue 268 using suction through suction port 278. Tissueadhesive 296 is injected through injection channel 270 to coat and sealthe puncture wound in targeted tissue 268. Engagement catheter 254 isthen withdrawn, leaving a plug of tissue adhesive 296 attached to theatrial wall or atrial appendage.

Another example for sealing the puncture wound in the atrial wall orappendage is shown in FIGS. 15A, 15B, and 15C. A sandwich-type closuremember, having an external cover 610 and an internal cover 620, isinserted through the lumen of engagement catheter 600, which is attachedto the targeted tissue of an atrial wall 630. Each of external andinternal covers 610 and 620 is similar to an umbrella in that it can beinserted through a catheter in its folded configuration and expanded toan expanded configuration once it is outside of the catheter. As shownin FIG. 15A, external cover 610 is deployed (in its expandedconfiguration) on the outside of the atrial wall to seal a puncturewound in the targeted tissue, having already been delivered through thepuncture wound into the pericardial space. Internal cover 620 isdelivered through engagement catheter 600 (in its folded configuration),as shown in FIGS. 15A and 15B, by an elongated delivery wire 615, towhich internal cover 620 is reversibly attached. Once internal cover 620is in position on the inside of atrial wall 630 at the targeted tissue,internal cover 620 is deployed to help seal the puncture wound in thetargeted tissue (see FIG. 15C). Engagement catheter 600 then releasesits grip on the targeted tissue and is withdrawn, leaving thesandwich-type closure to seal the puncture wound, as shown in FIG. 15C.External cover 610 and internal cover 620 may be held in place usingadhesion. Similarly, external cover 610 and internal cover 620 may beheld in place using magnetic forces, such as, for example, by the insideface (not shown) of external cover 610 comprising a magnet, by theinside face (not shown) of internal cover 620 comprising a magnet, orboth inside faces of external cover 610 or internal cover 620 comprisinga magnet.

FIGS. 16A, 16B, 16C, and 16D show another embodiment of an engagementcatheter as disclosed herein. Engagement catheter 700 is an elongatedtube having a proximal end 710 and a distal end 720, as well as twolumens 730, 740 extending between proximal end 710 and distal end 720.Lumens 730, 740 are formed by concentric inner wall 750 and outer wall760, as particularly shown in FIGS. 16B and 16C. At proximal end 710,engagement catheter 700 includes a vacuum port 770, which is attached tolumen 730 so that a vacuum source can be attached to vacuum port 770 tocreate suction in lumen 730, thereby forming a suction channel. Atdistal end 720 of catheter 700, a suction port 780 is attached to lumen730 so that suction port 780 can be placed in contact with heart tissue775 (see FIG. 16D) for aspirating the tissue, thereby forming a vacuumseal between suction port 780 and tissue 775 when the vacuum source isattached and engaged. The vacuum seal enables suction port 780 to grip,stabilize, and retract tissue 775. For example, attaching a suction portto an interior atrial wall using a vacuum source enables the suctionport to retract the atrial wall from the pericardial sac surrounding theheart, which enlarges the pericardial space between the atrial wall andthe pericardial sac.

As shown in FIG. 16C, two internal lumen supports 810, 820 are locatedwithin lumen 730 and are attached to inner wall 750 and outer wall 760to provide support to the walls. These lumen supports divide lumen 730into two suction channels. Although internal lumen supports 810, 820extend from distal end 720 of catheter 700 along a substantial portionof the length of catheter 700, internal lumen supports 810, 820 may ormay not span the entire length of catheter 700. Indeed, as shown inFIGS. 16A, 16B, and 16C, internal lumen supports 810, 820 do not extendto proximal end 710 to ensure that the suction from the external vacuumsource is distributed relatively evenly around the circumference ofcatheter 700. Although the embodiment shown in FIG. 16C includes twointernal lumen supports, other embodiments may have just one internalsupport or even three or more such supports.

FIG. 16D shows engagement catheter 700 approaching heart tissue 775 forattachment thereto. It is important for the clinician performing theprocedure to know when the suction port has engaged the tissue of theatrial wall or the atrial appendage. For example, in reference to FIG.16D, it is clear that suction port 780 has not fully engaged tissue 775such that a seal is formed. However, because suction port 780 is notusually seen during the procedure, the clinician may determine when theproper vacuum seal between the atrial tissue and the suction port hasbeen made by monitoring the amount of blood that is aspirated, bymonitoring the suction pressure with a pressure sensor/regulator, orboth. For example, as engagement catheter 700 approaches the atrial walltissue (such as tissue 775) and is approximately in position, thesuction can be activated through lumen 730. A certain level of suction(e.g., 10 mmHg) can be imposed and measured with a pressuresensor/regulator. As long as catheter 700 does not engage the wall, someblood will be aspirated into the catheter and the suction pressure willremain the same. However, when catheter 700 engages or attaches to thewall of the heart (depicted as tissue 775 in FIG. 16D), minimal blood isaspirated and the suction pressure will start to gradually increase.Each of these signs can alert the clinician (through alarm or othermeans) as an indication of engagement. The pressure regulator is thenable to maintain the suction pressure at a preset value to preventover-suction of the tissue.

An engagement catheter, such as engagement catheter 700, may beconfigured to deliver a fluid or other substance to tissue on the insideof a wall of the heart, including an atrial wall or a ventricle wall.For example, lumen 740 shown in FIGS. 16A and 16C includes an injectionchannel 790 at distal end 720. Injection channel 790 dispenses to thetargeted tissue a substance flowing through lumen 740. As shown in FIG.16D, injection channel 790 is the distal end of lumen 740. However, inother embodiments, the injection channel may be ring-shaped (see FIG.13C) or have some other suitable configuration.

Substances that can be locally administered with an engagement catheterinclude preparations for gene or cell therapy, drugs, and adhesives thatare safe for use in the heart. The proximal end of lumen 740 has a fluidport 800, which is capable of attachment to an external fluid source forsupply of the fluid to be delivered to the targeted tissue. Indeed,after withdrawal of a needle from the targeted tissue, as discussedherein, an adhesive may be administered to the targeted tissue by theengagement catheter for sealing the puncture wound left by the needlewithdrawn from the targeted tissue.

Referring now to FIGS. 17A, 17B, and 17C, there is shown a deliverycatheter 850 comprising an elongated hollow tube 880 having a proximalend 860, a distal end 870, and a lumen 885 along the length of thecatheter. Extending from distal end 870 is a hollow needle 890 incommunication with lumen 885. Needle 890 is attached to distal end 870in the embodiment of FIGS. 17A, 17B, and 17C, but, in other embodiments,the needle may be removably attached to, or otherwise located at, thedistal end of the catheter (see FIG. 12A). In the embodiment shown inFIGS. 17A, 17B, and 17C, as in certain other embodiments having anattached needle, the junction (i.e., site of attachment) between hollowtube 880 and needle 890 forms a security notch 910 circumferentiallyaround needle 890 to prevent needle 890 from over-perforation. Thus,when a clinician inserts needle 890 through an atrial wall to gainaccess to the pericardial space, the clinician will not, under normalconditions, unintentionally perforate the pericardial sac with needle890 because the larger diameter of hollow tube 880 (as compared to thatof needle 890) at security notch 910 hinders further needle insertion.Although security notch 910 is formed by the junction of hollow tube 880and needle 890 in the embodiment shown in FIGS. 17A, 17B, and 17C, otherembodiments may have a security notch that is configured differently.For example, a security notch may include a band, ring, or similardevice that is attached to the needle a suitable distance from the tipof the needle. Like security notch 910, other security notch embodimentshinder insertion of the needle past the notch itself by presenting alarger profile than the profile of the needle such that the notch doesnot easily enter the hole in the tissue caused by entry of the needle.

It is useful for the clinician performing the procedure to know when theneedle has punctured the atrial tissue. This can be done in severalways. For example, the delivery catheter can be connected to a pressuretransducer to measure pressure at the tip of the needle. Because thepressure is lower and much less pulsatile in the pericardial space thanin the atrium, the clinician can recognize immediately when the needlepasses through the atrial tissue into the pericardial space.

Alternatively, as shown in FIG. 17B, needle 890 may be connected to astrain gauge 915 as part of the catheter assembly. When needle 890contacts tissue (not shown), needle 890 will be deformed. Thedeformation will be transmitted to strain gauge 915 and an electricalsignal will reflect the deformation (through a classical wheatstonebridge), thereby alerting the clinician. Such confirmation of thepuncture of the wall can prevent over-puncture and can provideadditional control of the procedure.

In some embodiments, a delivery catheter, such as catheter 850 shown inFIGS. 17A, 17B, and 17C, is used with an engagement catheter, such ascatheter 700 shown in FIGS. 16A, 16B, 16C, and 16D, to gain access tothe pericardial space between the heart wall and the pericardial sac.For example, engagement catheter 700 may be inserted into the vascularsystem and advanced such that the distal end of the engagement catheteris within the atrium. The engagement catheter may be attached to thetargeted tissue on the interior of a wall of the atrium using a suctionport as disclosed herein. A standard guide wire may be inserted throughthe lumen of the delivery catheter as the delivery catheter is insertedthrough the inner lumen of the engagement catheter, such as lumen 740shown in FIGS. 16B and 16C. Use of the guide wire enables more effectivenavigation of the delivery catheter 850 and prevents the needle 890 fromdamaging the inner wall 750 of the engagement catheter 700. When the tipof the delivery catheter with the protruding guide wire reaches theatrium, the wire is pulled back, and the needle is pushed forward toperforate the targeted tissue. The guide wire is then advanced throughthe perforation into the pericardial space, providing access to thepericardial space through the atrial wall.

Referring again to FIGS. 17A, 17B, and 17C, lumen 885 of deliverycatheter 850 may be used for delivering fluid into the pericardial spaceafter needle 890 is inserted through the atrial wall or the atrialappendage. After puncture of the wall or appendage, a guide wire (notshown) may be inserted through needle lumen 900 into the pericardialspace to maintain access through the atrial wall or appendage. Fluid maythen be introduced to the pericardial space in a number of ways. Forexample, after the needle punctures the atrial wall or appendage, theneedle is generally withdrawn. If the needle is permanently attached tothe delivery catheter, as in the embodiment shown in FIGS. 17A and 17B,then delivery catheter 850 would be withdrawn and another deliverycatheter (without an attached needle) would be introduced over the guidewire into the pericardial space. Fluid may then be introduced into thepericardial space through the lumen of the second delivery catheter.

In some embodiments, however, only a single delivery catheter is used.In such embodiments, the needle is not attached to the deliverycatheter, but instead may be a needle wire (see FIG. 12A). In suchembodiments, the needle is withdrawn through the lumen of the deliverycatheter, and the delivery catheter may be inserted over the guide wireinto the pericardial space. Fluid is then introduced into thepericardial space through the lumen of the delivery catheter.

The various embodiments disclosed herein may be used by clinicians, forexample: (1) to deliver genes, cells, drugs, etc.; (2) to providecatheter access for epicardial stimulation; (3) to evacuate fluidsacutely (e.g., in cases of pericardial tampondae) or chronically (e.g.,to alleviate effusion caused by chronic renal disease, cancer, etc.);(4) to perform transeptal puncture and delivery of a catheter throughthe left atrial appendage for electrophysiological therapy, biopsy,etc.; (5) to deliver a magnetic glue or ring through the right atrialappendage to the aortic root to hold a percutaneous aortic valve inplace; (6) to deliver a catheter for tissue ablation, e.g., to thepulmonary veins, or right atrial and epicardial surface of the heart foratrial and ventricular arrythmias; (7) to deliver and place epicardial,right atrial, and right and left ventricle pacing leads (as discussedherein); (8) to occlude the left atrial appendage through percutaneousapproach; and (9) to visualize the pericardial space with endo-camera orscope to navigate the epicardial surface of the heart for therapeuticdelivery, diagnosis, lead placement, mapping, etc. Many otherapplications, not explicitly listed here, are also possible and withinthe scope of the present disclosure.

Referring now to FIG. 18, there is shown a cardiac tissue 1000 having afirst surface 1010 and an opposing surface 1020. First surface 1010comprises an epicardial surface of the heart, while opposing surface1020 comprises an endocardial surface of the heart. An external catheter1030 is shown being used in conjunction with an internal catheter 1060to perform ablation on the epicardial surface of the heart. Externalcatheter 1030 comprises a distal end 1035, a first magnet 1040positioned at distal end 1035 of external catheter 1030, and an ablationcontact 1050 positioned at distal end 1035 of external catheter 1030.Ablation contact 1050 is configured to remove or destroy tissue bycontacting the tissue and emitting radiofrequency energy into thetissue. However, other embodiments of ablation contacts may destroytissue using electrical energy, intense cold (cryoablation), or anyother suitable method.

Internal catheter 1060 comprises a distal end 1065 and a first magnet1070 positioned at distal end 1065 of internal catheter 1060. Firstmagnet 1070 comprises a traditional magnet, also known as a permanentmagnet or ferromagnet. As shown in FIG. 18, first magnet 1070 issphere-like in shape, but other embodiments of magnets may be of othersuitable shapes. In addition, unlike the embodiment of FIG. 18, at leastsome embodiments of magnets comprise, instead of a permanent magnet, anelectrode that is capable of acting as an electromagnet. Such electrodesare capable of transitioning between a magnetized state, in which theelectrode emits a magnetic field capable of attracting other magnets,and a nonmagnetized state, in which the electrode does not emit anysignificant magnetic field. Such electrodes are connected to a powersource and can be transitioned to the magnetized state or to thenonmagnetized state by switching the power on and off, respectively, orby any other method.

In the embodiment shown in FIG. 18, first magnet 1040 of externalcatheter 1030 comprises a permanent magnet. However, at least some otherembodiments of the first magnet of the external catheter may comprise anelectrode rather than a permanent magnet. Such electrodes act aselectromagnets. Thus, for example, where the first magnet of theexternal catheter comprises a first electrode, the first electrode iscapable of transitioning between a magnetized state, in which theelectrode attracts the first magnet of the internal catheter, and anonmagnetized state, in which the electrode does not significantlyattract the first magnet of the internal catheter. This transitionbetween the magnetized and nonmagnetized states may be accomplished bysupplying and removing electric current to the electrode.

As shown in FIG. 18, portions of external catheter 1030, specificallyablation contact 1050 and first magnet 1040 of external catheter 1030,are positioned on first surface 1010 of tissue 1000. A portion ofinternal catheter 1060, specifically first magnet 1070 of internalcatheter 1060, is positioned on opposing surface 1020 of tissue 1000.Internal catheter 1060 is configured for engaging external catheter 1030in this position such that the clinician's manipulation of internalcatheter 1060 can direct external catheter 1030. Specifically, in theembodiment shown in FIG. 18, the magnetic field emitted by first magnet1070 of internal catheter 1060 engages first magnet 1040 of externalcatheter 1030, thereby attracting first magnet 1040 of external catheter1030 such that distal end 1035 of external catheter 1030 is pulled alongfirst surface 1010 toward the position of first magnet 1070 of internalcatheter 1060. Thus, as the clinician moves distal end 1065 of internalcatheter 1060 along opposing surface 1020, distal end 1035 of externalcatheter 1030 is directed toward a desired location on first surface1010.

While the embodiment of FIG. 18 includes an external catheter havingonly one magnet, at least some other embodiments of external cathetershave a plurality of magnets, such as a second magnet comprising a secondelectrode. Indeed, other embodiments of external catheter may have athird electrode, or even more electrodes. Each such electrode ispositioned at or near the distal end of the external catheter, and eachis capable of transitioning between a magnetized state, in which itattracts a magnet of the internal catheter, and a nonagnetized state, inwhich the electrode does not significantly attract the magnet of theinternal catheter.

Likewise, at least some other embodiments of internal catheters may havea plurality of magnets. For example, FIG. 19 shows an internal catheter1110 having multiple magnets. Tissue 1100 has a first surface 1104,which is an epicardial surface of a heart, and an opposing surface 1106,which is an endocardial surface of the heart. An external catheter 1120comprises a first magnet 1130 and an ablation contact 1140, each ofwhich is positioned at distal end 1125 of external catheter 1120. Asshown in FIG. 19, ablation contact 1140 is in contact with surface 1104.The path of the movement of ablation contact 1140 on surface 1104 isindicated by scarring 1150, which is the ablated tissue.

As noted, internal catheter 1110 includes a plurality of magnets. Afirst magnet 1160 comprises a first electrode capable of transitioningbetween a magnetized state, in which the electrode attracts first magnet1130 of external catheter 1120, and a nonmagnetized state, in which theelectrode does not significantly attract first magnet 1130 of externalcatheter 1120. First magnet 1160 of internal catheter 1110 does notsignificantly attract first magnet 1130 of external catheter 1120 ifexternal catheter 1120 cannot be moved by manipulation of internalcatheter 1110. Internal catheter further comprises a second magnetcomprising a second electrode 1170, a third magnet comprising a thirdelectrode 1180, a fourth magnet comprising a fourth electrode 1190, afifth magnet comprising a fifth electrode 1200, a sixth magnetcomprising a sixth electrode 1210, a seventh magnet comprising a seventhelectrode 1220, an eighth magnet comprising an eighth electrode 1230,and a ninth magnet comprising a ninth electrode 1240. Each electrodeacts as an electromagnet and is capable of transitioning between amagnetized state, in which the electrode attracts first magnet 1130 ofexternal catheter 1120, and a nonmagnetized state, in which theelectrode does not significantly attract first magnet 1130 of externalcatheter 1120. Each electrode is positioned at distal end 1115 ofinternal catheter 1110. However, at least some electrodes of at leastsome other embodiments may be positioned on the internal catheter nearthe distal end of the internal catheter, so long as each of theelectrodes can be inserted into the patient's heart (or other body lumenof interest) adjacent to the tissue to be ablated or otherwise treated.

As shown, internal catheter 1110 forms a loop within the heart (i.e., onthe endocardial side of the cardiac tissue) such that each electrode islocated within the heart. In at least some embodiments, the loop may beformed in the catheter within the heart.

Although internal catheter 1110 comprises nine electrodes, otherembodiments of internal catheters may have almost any number ofelectrodes (for example, from one electrode to twelve electrodes ormore), depending on the intended use of the internal catheter.

Various embodiments of internal and external catheters may be used withan engagement catheter, as disclosed herein. In such embodiments, theexternal catheter, and optionally the internal catheter, would beconfigured for at least partial insertion into the second lumen of theengagement catheter (see, e.g., FIG. 13A). Any internal or externalcatheters to be delivered to the relevant treatment site through theengagement catheter must be sized and shaped to fit within theengagement catheter lumen.

However, depending on the location of the tissue targeted for ablation,the internal catheter may need to access locations on the endocardialsurface of the heart that are inaccessible from within the engagementcatheter. In such cases, the internal catheter may be placed in theheart without use of the engagement catheter. Thus, to place theinternal catheter at the proper location within the heart, cliniciansmay use radiography to visualize the catheter and the cardiac anatomy,or various other localization techniques may be used.

For example, a clinician may direct the placement of the internalcatheter using data collected with an impedance catheter, as discussedherein.

Referring now to FIG. 20, there is shown distal end 1155 of an internalcatheter 1150 comprising a first electrode 1160 positioned at distal end1155, a second electrode 1170 positioned at distal end 1155, a thirdelectrode 1174 positioned at distal end 1155, a fourth electrode 1176positioned at distal end 1155, a pair of excitation electrodes 1180 and1184 positioned at distal end 1155, and a pair of detection electrodes1190 and 1194 positioned on internal catheter 1150 between excitationelectrodes 1180 and 1184. Using the pair of excitation electrodes andthe pair of detection electrodes, the anatomical structure of the insideof the heart can be determined, as disclosed herein, leading to moreaccurate placement of internal catheter 1150 prior to ablation. Afterinternal catheter 1150 is correctly placed, electrodes 1160, 1170, 1174,and 1176 are used to engage an external catheter and direct an ablationcontact on the external catheter across the epicardial surface of theheart, as discussed herein.

Using the catheter embodiments disclosed herein, a clinician cannavigate an ablation catheter into the pericardial space, and thereforecan ablate the epicardial surface of the heart, by engaging the ablationcatheter with an internal catheter inside the heart. The pericardialspace can be accessed using an engagement catheter, such as, forexample, engagement catheter 700 shown in FIGS. 16A, 16B, 16C, and 16D.In addition, the internal catheter may be navigated within the bloodvessels and heart, as disclosed herein.

For example, an external catheter (such as external catheter 1120 ofFIG. 19), an internal catheter (such as internal catheter 1110 of FIG.19), and an engagement catheter (such as engagement catheter 700 of FIG.16A) are provided. Engagement catheter 700 is inserted into the heartand suction is initiated to aspirate the cardiac tissue from thesurrounding pericardial sac (see, e.g., FIG. 13B). A perforation of thetissue is made, for example, with a needle advanced through one of thelumens (e.g., lumen 740) of engagement catheter 700, and a guide wire isinserted through the hole in the cardiac tissue into the pericardialspace, thereby providing access to the pericardial space. Distal end1125 of external catheter 1120 (shown in FIG. 19), is guided into thepericardial space and is placed adjacent to the epicardial surface ofthe heart. Distal end 1115 of internal catheter 1110 is guided into theinterior of the heart and placed adjacent to an opposing surface of theheart (i.e., the endocardial surface of the heart).

Internal catheter 1110 is manipulated to direct ablation contact 1140 ofexternal catheter 1120 to contact a first targeted location on theepicardial surface of the heart. When the ablation contact is activated,ablation of the first targeted location occurs.

Manipulation of the internal catheter to direct the ablation contact canoccur in a number of ways. For example, referring to FIG. 18, bybringing magnet 1070 of internal catheter 1060 into sufficient proximityto magnet 1040 of external catheter 1030, magnet 1070 of internalcatheter 1060 engages magnet 1040 of external catheter 1030 (if bothmagnets are activated). Internal catheter 1060 can then be moved alongthe endocardial surface 1020 of cardiac tissue 1000 and, because of themagnetic engagement between the internal and external catheters,ablation contact 1050 of external catheter 1030 will move along theepicardial surface 1010 of cardiac tissue 1000. In other words, theablation contact will follow essentially the same path along theepicardial surface that the magnet of the internal catheter followsalong the endocardial surface of the heart. This technique can be usedto place the ablation contact on the precise location of the epicardialsurface targeted for ablation. In such a case, the ablation contact isactivated only when it is properly positioned; it may then bedeactivated after ablation is complete. However, the ablation contactmay remain activated while the external catheter is moved to a secondtargeted location on the epicardial surface of the heart. In this case,the tissue is ablated not only at the first and second targetedlocations, but also along the path the ablation contact took when itmoved from the first targeted location to the second targeted location.

An internal catheter having a multiplicity of magnets comprisingelectrodes may be manipulated to direct the ablation contact in otherways. For example, when using a catheter with a multiplicity ofelectrodes, such as internal catheter 1110 shown in FIG. 19, theclinician may not need to move the internal catheter after the ablationcontact of the external catheter is placed at the first targetedlocation on the epicardial surface of the heart. After the ablationcontact is directed to the first targeted location and ablation isaccomplished at the first targeted location, the ablation contact may bedirected solely by manipulation of the electrodes on the internalcatheter. For example, referring to FIG. 19, ablation contact 1140 maybe directed across surface 1104 by activating and deactivating theelectrodes on internal catheter 1110. If magnet 1130 of externalcatheter 1120 is engaged by first electrode 1160, then first electrode1160 is deactivated by switching first electrode 1160 to thenonmagnetized state. Second electrode 1170 is then activated byswitching second electrode 1170 to the magnetized state, therebyattracting first magnet 1130 of external catheter 1120 (and thereforeablation contact 1140) to the second targeted location on surface 1140.If ablation contact 1140 is active during the movement of the externalcatheter, then the tissue between the first targeted location and thesecond targeted location will be ablated (see, e.g., scarring 1150).After ablation contact 1140 reaches the second targeted location, secondelectrode 1170 is switched to the nonmagnetized state and thirdelectrode 1180 is switched to the magnetized state, moving ablationcontact 1140 to the third targeted location. This process is thenrepeated through the desired number of electrodes until the ablation iscomplete.

Where the internal catheter is sufficiently flexible, the catheter maybe positioned in a loop within the heart such that the electrodes form acircumference (see, e.g., FIG. 19). Alternatively, a loop may bepreformed in the catheter and delivered to the inside of the heart.Regardless, the circumference predefines the region to be ablated. Theablation contact of the external catheter is directed by the sequentialactivation and deactivation of electrodes, as described above, such thatthe path of ablation follows the circumference formed by the electrodes.In other words, once ablation is completed at one location, the magneticfield is turned off at that point and turned on at the adjacent point,thereby moving the external catheter (and therefore the ablationcontact) into a new position along the circumference. This method ofablation may be especially useful for ablating around a pulmonary vein(i.e., at the pulmonary vein-atrial junction).

Certain of the disclosed embodiments have been shown having an externalcatheter with an ablation contact and an internal catheter that is usedto direct the external catheter. However, at least some otherembodiments have an ablation contact on an internal catheter that isdirected by manipulation of the external catheter.

While various embodiments of systems and methods for navigating acatheter along the epicardial surface of the heart have been describedin considerable detail herein, the embodiments are merely offered by wayof non-limiting examples of the invention described herein. Manyvariations and modifications of the embodiments described herein will beapparent to one of ordinary skill in the art in light of the thisdisclosure. It will therefore be understood by those skilled in the artthat various changes and modifications may be made, and equivalents maybe substituted for elements thereof, without departing from the scope ofthe invention. Indeed, this disclosure is not intended to be exhaustiveor to limit the scope of the invention. The scope of the invention is tobe defined by the appended claims, and by their equivalents.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described. Asone of ordinary skill in the art would appreciate, other sequences ofsteps may be possible. Therefore, the particular order of the stepsdisclosed herein should not be construed as limitations on the claims.In addition, the claims directed to a method and/or process should notbe limited to the performance of their steps in the order written, andone skilled in the art can readily appreciate that the sequences may bevaried and still remain within the spirit and scope of the presentinvention.

It is therefore intended that the invention will include, and thisdescription and the appended claims will encompass, all modificationsand changes apparent to those of ordinary skill in the art based on thisdisclosure.

1. A system for use with a vacuum source for ablating a tissue of aheart, comprising: an engagement catheter comprising a proximal end, adistal end, and first and second lumens extending between the proximalend and the distal end; an external catheter comprising a distal end, anablation contact positioned at or near the distal end of the externalcatheter, and a first magnet positioned at or near the distal end of theexternal catheter, wherein the external catheter is configured such thatthe external catheter is capable of at least partial insertion into thesecond lumen of the engagement catheter; an internal catheter comprisinga distal end and a first magnet positioned at or near the distal end ofthe internal catheter, the internal catheter devoid of an ablationcontact; and a vacuum port located at the proximal end of the engagementcatheter, the vacuum port being operatively connected to the first lumenof the engagement catheter and capable of operative connection to thevacuum source; wherein the first lumen of the engagement catheterincludes a suction port located at or near the distal end of theengagement catheter, the suction port being configured to removablyattach to a targeted tissue on the interior of a wall of the heart, suchthat the suction port is capable of forming a reversible seal with thetargeted tissue when the vacuum source is operatively attached to thevacuum port, wherein the internal catheter is configured for engagingthe external catheter when a portion of the external catheter ispositioned on or adjacent to an epicardial surface of the heart and aportion of the internal catheter is positioned on or adjacent to anendocardial surface of the heart, such that manipulation of the internalcatheter is capable of directing the external catheter, and wherein thesystem is capable of enlarging a pericardial space between the targetedtissue and a pericardial sac that surrounds the heart by retracting thetargeted tissue away from the pericardial sac; and wherein the internalcatheter is configured for engaging the external catheter when a portionof the external catheter is positioned on or adjacent to the epicardialsurface of the heart and a portion of the internal catheter ispositioned on or adjacent the endocardial surface of the heart, suchthat manipulation of the internal catheter is capable of directing theexternal catheter so that the external catheter is operable to remove ordestroy tissue at the first surface of the tissue at a location directedby the internal catheter; and wherein the external catheter is furtheroperable to remove or destroy tissue at the epicardial surface at asecond location directed by the internal catheter and along theepicardial surface between the first location and the second locationwithout moving the internal catheter.
 2. The system of claim 1, wherein:the internal catheter further comprises a second magnet; the firstmagnet of the internal catheter comprises a first electrode capable oftransitioning between a magnetized state, in which the first electrodeattracts the first magnet of the external catheter, and a nonmagnetizedstate, in which the first electrode does not significantly attract thefirst magnet of the external catheter; and the second magnet of theinternal catheter comprises a second electrode capable of transitioningbetween a magnetized state, in which the second electrode attracts thefirst magnet of the external catheter, and a nonmagnetized state, inwhich the second electrode does not significantly attract the firstmagnet of the external catheter.
 3. The system of claim 2, wherein: theinternal catheter further comprises a pair of excitation electrodespositioned at or near the distal end of the internal catheter and a pairof detection electrodes positioned on the internal catheter between thepair of the excitation electrodes; and a proximal end of each of thepair of excitation electrodes and each of the pair of detectionelectrodes is connected to a processor, the processor being capable ofcollecting conductance data.
 4. The system of claim 3, wherein: theconductance data comprises a first conductance value determined at eachof a plurality of locations when the excitation electrodes and detectionelectrodes are immersed in a first fluid with a first conductivity and asecond conductance value determined at each of the plurality oflocations when the excitation electrodes and detection electrodes areimmersed in a second fluid with a second conductivity; and the firstconductivity does not equal the second conductivity.
 5. The system ofclaim 4, wherein: the internal catheter further comprises a thirdelectrode, the third electrode is positioned at or near the distal endof the internal catheter and the third electrode is capable oftransitioning between a magnetized state, in which the third electrodeattracts the first magnet of the external catheter, and a nonmagnetizedstate, in which the third electrode does not significantly attract thefirst magnet of the external catheter; and the internal catheter iscapable of forming a loop within the heart such that the first, second,and third electrodes are located within the heart.
 6. The system ofclaim 5, wherein: the internal catheter further comprises a fourthelectrode, the fourth electrode is positioned at or near the distal endof the internal catheter, the fourth electrode is capable oftransitioning between a magnetized state, in which the fourth electrodeattracts the first magnet of the external catheter, and a nonmagnetizedstate, in which the fourth electrode does not significantly attract thefirst magnet of the external catheter; and the internal catheter iscapable of forming a loop within the heart such that the first, second,third, and fourth electrodes are located within the heart.
 7. A systemfor navigating a catheter on a surface of a tissue, the systemcomprising: an external catheter comprising a distal end, a first magnetpositioned at or near the distal end of the external catheter, and anablation contact positioned at or near the distal end of the externalcatheter, the ablation contact being configured to remove or destroytissue; and an internal catheter comprising a distal end and a firstmagnet positioned at or near the distal end of the internal catheter,the internal catheter devoid of an ablation contact; wherein theinternal catheter is configured for engaging the external catheter whena portion of the external catheter is positioned on or adjacent to afirst surface of the tissue and a portion of the internal catheter ispositioned on or adjacent to an opposing surface of the tissue, suchthat manipulation of the internal catheter is capable of directing theexternal catheter so that the external catheter is operable to remove ordestroy tissue at the first surface of the tissue at a location directedby the internal catheter, and wherein the external catheter is furtheroperable to remove or destroy tissue at the first surface at a secondlocation directed by the internal catheter and along the first surfacebetween the first location and the second location without moving theinternal catheter.
 8. The system of claim 7, wherein: the first surfaceof the tissue comprises an epicardial surface of a heart; and theopposing surface of the tissue comprises an endocardial surface of theheart.
 9. The system of claim 7, wherein: the first magnet of theinternal catheter comprises a first electrode capable of transitioningbetween a magnetized state, in which the first electrode attracts thefirst magnet of the external catheter, and a nonmagnetized state, inwhich the first electrode does not significantly attract the firstmagnet of the external catheter.
 10. The system of claim 9, wherein: theinternal catheter further comprises a second electrode positioned at ornear the distal end of the internal catheter, the second electrode ofthe internal catheter being capable of transitioning between amagnetized state, in which the second electrode attracts the firstmagnet of the external catheter, and a nonmagnetized state, in which thesecond electrode does not significantly attract the first magnet of theexternal catheter.
 11. The system of claim 10, wherein: the internalcatheter further comprises a third electrode, the third electrode, ispositioned at or near the distal end of the internal catheter and thethird electrode is capable of transitioning between a magnetized state,in which the third electrode attracts the first magnet of the externalcatheter, and a nonmagnetized state, in which the third electrode doesnot significantly attract the first magnet of the external catheter; andthe internal catheter is capable of forming a loop within the heart suchthat the first, second, and third electrodes are located within theheart.
 12. The system of claim 11, wherein: the internal catheterfurther comprises a fourth electrode, the fourth electrode is positionedat or near the distal end of the internal catheter, the fourth electrodeis capable of transitioning between a magnetized state, in which thefourth electrode attracts the first magnet of the external catheter, anda nonmagnetized state, in which the fourth electrode does notsignificantly attract the first magnet of the external catheter; and theinternal catheter is capable of forming a loop within the heart suchthat the first, second, third, and fourth electrodes are located withinthe heart.
 13. The system of claim 7, wherein: the internal catheterfurther comprises a pair of excitation electrodes positioned at or nearthe distal end of the internal catheter and a pair of detectionelectrodes positioned on the internal catheter between the pair of theexcitation electrodes; and a proximal end of each of the pair ofexcitation electrodes and each of the pair of detection electrodes isconnected to a processor, the processor being capable of collectingconductance data and further capable of determining a profile of a bodylumen based upon conductance data obtained using the pair of detectionelectrodes in connection with at least one fluid injection.
 14. Thesystem of claim 6, wherein: the internal catheter further comprises apassageway for passing a fluid through the internal catheter to the bodylumen; and the conductance data is determined at each of a plurality oflocations.
 15. The system of claim 14, wherein: the conductance datacomprises a first conductance value determined at each of the pluralityof locations when the excitation electrodes and detection electrodes areimmersed in a first fluid with a first conductivity and a secondconductance value determined at each of the plurality of locations whenthe excitation electrodes and detection electrodes are immersed in asecond fluid with a second conductivity; and the first conductivity doesnot equal the second conductivity.
 16. The system of claim 7, wherein:the first magnet of the external catheter comprises a first electrodecapable of transitioning between a magnetized state, in which the firstelectrode attracts the first magnet of the internal catheter, and anonmagnetized state, in which the first electrode does not significantlyattract the first magnet of the internal catheter.
 17. The system ofclaim 16, wherein: the external catheter further comprises a secondelectrode positioned at or near the distal end of the external catheter,the second electrode of the external catheter being capable oftransitioning between a magnetized state, in which the second electrodeattracts the first magnet of the internal catheter, and a nonmagnetizedstate, in which the second electrode does not significantly attract thefirst magnet of the internal catheter.
 18. The system of claim 7,wherein: the external catheter further comprises a second magnetpositioned at or near the distal end of the external catheter.
 19. Amethod of ablating a targeted tissue on an epicardial surface of aheart, comprising: providing an external catheter comprising a distalend, a first magnet positioned at the distal end of the externalcatheter, and an ablation contact positioned at the distal end of theexternal catheter, wherein the ablation contact is configured to removeor destroy tissue; providing an internal catheter comprising a distalend, a first electrode positioned at or near the distal end of theinternal catheter, and a second electrode positioned at or near thedistal end of the internal catheter, the internal catheter devoid of anablation contact; placing the distal end of the internal catheter withinthe heart, such that the first and second electrodes are positionedwithin the heart at a desired ablation location and in a desiredablation pattern; activating the first electrode of the internalcatheter such that the ablation contact of the external catheter isdirected to the targeted tissue at a first location; activating theablation contact to ablate the targeted tissue using the externalcatheter at a location directed by the internal catheter; deactivatingthe first electrode of the internal catheter; and activating the secondelectrode of the internal catheter such that the ablation contact of theexternal catheter is directed to the targeted tissue at a secondlocation; wherein the targeted tissue is ablated by the ablation contactbetween the first location and the second location without relocatingthe internal catheter.
 20. The method of claim 19, further comprising:extending into a blood vessel an elongated tube having a proximal end, adistal end, and a first lumen, such that the distal end of the tube isin contact with a targeted tissue on the interior of a wall of theheart; aspirating the targeted tissue on the interior of the wall of theheart such that the wall of the heart is retracted away from apericardial sac surrounding the heart to enlarge a pericardial spacebetween the pericardial sac and the wall of the heart; accessing thepericardial space through the targeted tissue; and inserting at leastthe distal end of the external catheter into the pericardial space. 21.The method of claim 20, further comprising: introducing an impedancecatheter into the heart; measuring a first conductance value at a firstlocation in the heart; and measuring a second conductance value at asecond location in the heart.
 22. The method of claim 21, furthercomprising: determining a profile of a body lumen using the conductancedata.
 23. A method of ablating a tissue, the method comprising:providing an external catheter comprising a distal end, a first magnetpositioned at or near the distal end of the external catheter, and anablation contact positioned at or near the distal end of the externalcatheter, the ablation contact being configured to remove or destroytissue; providing an internal catheter comprising a distal end and afirst magnet positioned at or near the distal end of the internalcatheter, the internal catheter being configured for engaging theexternal catheter, the internal catheter devoid of an ablation contact;placing the distal end of the external catheter adjacent to a firstsurface of the tissue; placing the distal end of the internal catheteradjacent to an opposing surface of the tissue; manipulating the internalcatheter to direct the ablation contact of the external catheter tocontact a first targeted location on the first surface of the tissue;ablating the first targeted location on the first surface of the tissueusing the external catheter at a location directed by the internalcatheter; and ablating a second targeted location on the first surfaceof the tissue and along the first surface between the first location andthe second location without moving the internal catheter.
 24. The methodof claim 23, wherein: the tissue comprises cardiac tissue; the firstsurface of the tissue comprises an epicardial surface of the cardiactissue; and the opposing surface of the tissue comprises an endocardialsurface of the cardiac tissue.
 25. The method of claim 24, wherein: thestep of manipulating the internal catheter to direct the ablationcontact of the external catheter to contact a first targeted location onthe first surface of the tissue comprises (i) engaging the first magnetof the external catheter with the first magnet of the internal cathetersuch that moving the first magnet of the internal catheter moves thefirst magnet of the external catheter, (ii) moving the first magnet ofthe internal catheter along the endocardial surface of the cardiactissue such that the ablation contact of the external catheter movesalong the epicardial surface of the cardiac tissue to the first targetedlocation on the epicardial surface of the cardiac tissue.
 26. The methodof claim 24, wherein: the first magnet of the internal cathetercomprises a first electrode capable of transitioning between amagnetized state, in which the first electrode attracts the first magnetof the external catheter, and a nonmagnetized state, in which the firstelectrode does not significantly attract the first magnet of theexternal catheter.
 27. The method of claim 26, wherein: the step ofmanipulating the internal catheter to direct the ablation contact of theexternal catheter to contact a first targeted location on the firstsurface of the tissue comprises (i) engaging the first magnet of theexternal catheter with the first electrode of the internal catheter suchthat moving the first electrode of the internal catheter moves the firstmagnet of the external catheter, and (ii) moving the first electrode ofthe internal catheter along the endocardial surface of the cardiactissue such that the ablation contact of the external catheter movesalong the epicardial surface of the cardiac tissue to the first targetedlocation on the epicardial surface of the cardiac tissue.
 28. The methodof claim 27, further comprising the steps of: manipulating the internalcatheter to direct the ablation contact of the external catheter tocontact a second targeted location on the first surface of the tissue;and ablating the second targeted location on the first surface of thetissue.
 29. The method of claim 28, wherein: the step of manipulatingthe internal catheter to direct the ablation contact of the externalcatheter to contact a second targeted location on the first surface ofthe tissue further comprises (i) switching the first electrode of theinternal catheter to the nonmagnetized state, and (ii) switching thesecond electrode of the internal catheter to the magnetized state suchthat the ablation contact of the external catheter is moved to thesecond targeted location on the first surface of the tissue.
 30. Themethod of claim 29, further comprising: ablating the first surface ofthe tissue between the first targeted location on the first surface ofthe tissue and the second targeted location on the first surface of thetissue.
 31. The method of claim 30, wherein: the internal catheterfurther comprises a pair of excitation electrodes positioned at or nearthe distal end of the internal catheter and a pair of detectionelectrodes positioned on the internal catheter between the pair ofexcitation electrodes.
 32. The method of claim 31, wherein: the step ofmanipulating the internal catheter to direct the ablation contact of theexternal catheter to contact a first targeted location on the firstsurface of the tissue further comprises (i) measuring a firstconductance value at a first location, (ii) measuring a secondconductance value at a second location, and (iii) determining a profileof a body lumen based on the first conductance value and the secondconductance value.
 33. The method of claim 26, wherein: the step ofmanipulating the internal catheter to direct the ablation contact of theexternal catheter to contact a first targeted location on the firstsurface of the tissue comprises (i) positioning the first electrode ofthe internal catheter, (ii) switching the first electrode of theinternal catheter to the magnetized state such that the ablation contactof the external catheter is moved to the first targeted location on thefirst surface of the tissue.
 34. The method of claim 26, wherein: theinternal catheter further comprises a second electrode, the secondelectrode being capable of transitioning between a magnetized state, inwhich the second electrode attracts the magnet of the external catheter,and a nonmagnetized state, in which the second electrode does notsignificantly attract the magnet of the external catheter.
 35. Themethod of claim 34, wherein: the internal catheter further comprisesthird and fourth electrodes positioned at or near the distal end of theinternal catheter; and the internal catheter forms a loop within theheart, such that the first, second, third, and fourth electrodes arelocated within the heart.
 36. The method of claim 35, furthercomprising: ablating the first surface of the tissue in a specifiedcircumference, the circumference being approximately defined by the loopof the internal catheter.
 37. The method of claim 26, wherein: the firstmagnet of the external catheter comprises a first electrode.
 38. Themethod of claim 37, wherein: the external catheter further comprises asecond magnet positioned at or near the distal end of the externalcatheter.